Psychosocial and professional burden of Medically Assisted Reproduction (MAR): Results from a French survey

Blandine Courbiere; Arnaud Lacan; Michael Grynberg; Anne Grelat; Virginie Rio; Elisangela Arbo; Céline Solignac

doi:10.1371/journal.pone.0238945

. 2020 Sep 24;15(9):e0238945. doi: 10.1371/journal.pone.0238945

Psychosocial and professional burden of Medically Assisted Reproduction (MAR): Results from a French survey

Blandine Courbiere ^1,^2,^*, Arnaud Lacan ³, Michael Grynberg ⁴, Anne Grelat ⁵, Virginie Rio ⁶, Elisangela Arbo ⁷, Céline Solignac ⁷

Editor: Antonio Simone Laganà⁸

PMCID: PMC7514013 PMID: 32970695

Abstract

Objective

To evaluate the impact of infertility and Medically Assisted Reproduction (MAR) throughout all aspects of life among infertile women and men.

Materials and methods

An online survey included 1 045 French patients (355 men, 690 women) who were living or had lived the experience of infertility and MAR. The questionnaire included 56 questions on several domains: global feelings, treatment burden, rapport with medical staff, psychosocial impact, sexual life and professional consequences.

Results

Respondents had experienced an average of 3.6 (95% CI: 3.3–3.9) MAR cycles: 5% (n = 46) were pregnant, 4% (n = 47) were waiting to start MAR, 50% (n = 522) succeeded in having a live birth following MAR, 19% (n = 199) were currently undergoing ART, and 21% (n = 221) dropped out of the MAR process without a live birth. Satisfaction rates regarding the received medical care were above 80%, but 42% of patients pointed out the lack of information about non-medical support. An important impact on sexual life was reported, with 21% of patients admitted having not had intercourse for several weeks or even several months. Concerning the impact on professional life, 63% of active workers currently in an MAR program (n = 185) considered that MAR had strong repercussions on the organization of their working life with 49% of them reporting a negative impact on the quality of their work, and 46% of them reporting the necessity to lie about missing work during their treatment.

Conclusion

Despite a high overall level of satisfaction regarding medical care, the burden of infertility and MAR on quality of life is strong, especially on sexuality and professional organization. Clinical staff should be encouraged to develop non-medical support for all patients at any stage of infertility treatment. Enterprises should be warned about the professional impact of infertility and MAR to help their employees reconcile personal and professional life.

Introduction

Infertility is defined as the failure to achieve pregnancy after at least 12 months of regular unprotected sexual intercourse [1]. Infertility affects approximately 6% of US couples [2] and 10% to 20% of couples in Europe [3,4]. Since pioneering work was published in the early 1980s [5], a number of publications have shown that infertility is associated with many psychological and social consequences [6,7]. For infertile couples, a wide array of psychological issues has been described and measured [8,9], including but not limited to depression, anxiety, sexual dysfunction, and social isolation. Although not always strictly consistent, the vast majority of existing reports have demonstrated that both infertility and Medically Assisted Reproduction (MAR) procedures generate a substantial burden on infertile couples.

The last ESHRE and International Committee for Monitoring Assisted Reproductive Technology (ICMART) reports showed a continuing increase in the use of ART worldwide [10,11]. According to the ICMART data that reported about two-thirds of the worldwide ART activity, 1 643 912 ART cycles led to the birth of more than 394 662 babies in 2011 (data excluding Republic of China). ART activity in China has been estimated at 2 million cycles with 500 000 babies per year. In ART centers, ART outcome criteria such as the live birth rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome rate are closely monitored. Despite some tools as SCREENIVF have been validated for screening patient at risk of emotional distress after ART [12], the psychosocial consequences of ART still seem to be a lower priority as a center quality indicator than effectiveness and safety. In 2015, in ESHRE guideline, Gameiro et al. reported international recommendations for providing routine psychosocial care in infertility and medically assisted reproduction [13]. Psychosocial care could reduce stress about medical procedures and improve lifestyle. However, in real life, physicians specialized in reproductive medicine often haven’t sufficient available tools for offering personalized and adapted psychosocial care to patients involved in an ART process.

There are still gaps in the knowledge regarding individual perceptions and patient experiences of infertility and during the use of assisted reproduction technologies (ART). First, few studies have analyzed the entire impact of infertility and its management throughout the entire care pathway, namely, before, during and after ART procedures. Additionally, studies often focus on a specific aspect (i.e., sexual dysfunction [14]) and/or a time period in the reproductive life of couples: at the diagnosis of infertility, during the ART procedure [15], after ART drop out [16] or a long time after ART to study long-term outcome [17].Second, most studies focused on women, whereas there is little evidence regarding men’s reported problems within the course of the infertility journey [18]. Third, most published work uses either standardized general or disease-specific tools, yet those instruments may fail to capture some dimensions of mental health, and they may also limit the spontaneous expression of affected people. Last, we lack real-life data regarding actual management and patient experience.

In France, in public infertility treatment Units, fertility treatments and ART are free of charge for women until 43 years. The government health insurance covers 6 intrauterine inseminations and 4 IVF cycles per live birth, as well as the cost of absences from work for infertility treatment. For other health care costs (ex: psychologist, alternative and complementary medicine), patients can be refunded partially or totally by French government and private mutual insurers. In this context, the objective of our study was to collect perceptions of and real-life experiences of people treated for infertility with MAR treatments in a large sample of infertile French women and men throughout the entire process of their MAR program.

Materials and methods

A prospective cross-sectional web-based survey was conducted by Ipsos, the largest French company in market and public opinion research, from October 7th, 2018, to October 28th, 2018, targeting French patients with a prior or current history of infertility in any specialized healthcare facility. The overall study sample has been previously targeted and investigated throughout the Ipsos Access panel; the study sample is composed of 314 077 people in France who are representative of the French population. Females and males in the targeted sample pool who were aged over 18 and under 50 years received an email invitation describing the study and directing the recipients to the secure anonymous survey website. Before taking part in the survey, participants were given a detailed description of the study and asked to provide consent to participate. Regarding the recruitment and targeting of the people participating in this survey, extensive quality procedures were in place to ensure that the survey inputs allowed for high quality survey outputs. Panel respondents were required to validate their registration via a security code to prevent automatic registration, and they double-opted in via email confirmation to ensure validity of the email address provided. All email extensions of clients, competitors, and Ipsos employees were removed, mismatched device settings and Geo-IP locations were also removed. Patterns in names, emails, and IP addresses collected at registration, and accounts that had multiple elements in common were removed.

Eligible respondents also had not participated recently in similar surveys. Strict panel usage rules were established to avoid interviewing the same people too often and to prevent them from being used too often for any individual type of survey. Duplicate device identification is also in place through digital fingerprinting (RelevantID©) and web/flash cookies. Respondents could only take the survey once, and this was assured by duplicate contact details identification. During the investigation, inattentive respondents were identified and removed. To identify someone who displayed inattentive survey-taking behavior through completing a survey too quickly, the time spent in the survey overall was measured, as well as the number of answers provided. This allowed us to calculate a completion speed, the number of answers provided per minute, for each respondent. To identify someone who displayed inattentive survey-taking behavior by providing identical answers across multiple questions within and across multiple grids, straight-lining response patterns were measured.

Inclusion criteria were established with the scientific committee of the study (BC, MG, AG, CS, EA). Medically Assisted Reproduction (MAR) is defined by the international Glossary on Infertility and Fertility care [1] and include “ovulation induction, ovarian stimulation, ovulation triggering, all ART procedures, uterine transplantation and intra-uterine, intracervical, and intravaginal insemination with semen of husband/partner or donor. However, we excluded from our survey women who underwent ovulation induction, because they couldn’t report the burden of a laboratory intervention. People surveyed included males or females between 18 and 50 years old, currently undergoing a MAR procedure or having had an MAR procedure with or without a live birth (except those currently undergoing or having undergone MAR abroad).

The patient survey included a 56-point questionnaire developed for the study; the survey was completed and submitted online (See S1 and S2 Files: questionnaire available in French and in English). Because our objective was to provide an overview about the impact of infertility and MAR process throughout different aspects of the daily-life of patients, questions were elaborated by a scientific committee composed by physicians specialized in reproductive medicine, an Economic Doctor specialized in Human Resources and wellbeing at work (AL), and a representative (VR) from a National Infertility Association (bAMP) highly involved in France for supporting infertile couples. Before the survey, the questions were validated by infertile patients from bAMP Association. Questions were constructed both on existing literature (to validate data already described, as psychosocial impact) and on clinical experience reported both by physician and patients (as the professional impact, often described by patients).

The first part of the survey collected demographic and general information (age, sex, level of well-being, family status, history of MAR procedure or ongoing MAR procedure, type of MAR, number of attempts, etc.). The second part explored the respondents’ personal history before resorting to MAR (delay before consultation, feeling when difficulties to conceive were first discovered, health professionals who made the diagnosis, etc.). The third and fourth parts of the survey included questions regarding experience with and perception of MAR (global feelings, psychological and physical impacts, impact on affective and sexual life, impact on relationships with others, impact on professional life, treatment burden, rapport with medical staff, expectations, etc.). The overall well-being score was self-reported by a numeric scale with rates ranging from 0 to 10 (0 for very low well-being to 10 for very high well-being); the impact of MAR on different domains of life was evaluated from 0 to 10 (0 for very low impact to 10 for very high impact). Most questions had multiple answers, and the results were expressed as a percentage of each answer.

Data management and analyses

Statistical analyses and tests were performed using COSI software (M.L.I., 1994, France). Descriptive statistics include frequency tables, mean, standard deviations and 95% confidence interval (95% CI). A p value<0.05 was considered as significant for this statistical analysis. The current article focuses on highlighting the statistical differences between specific groups of population: people still undergoing MAR, people for whom MAR led to a live birth, people who dropped out of MAR, men and women. A system of letters has been implemented to illustrate the statistical differences between these subgroups. Letter B stands for people still undergoing MAR, letter C stands for people for whom MAR led to a live birth, letter D stands for People who dropped out of MAR, letter E stands for men and letter F stands for women. “+” refers to a superior significant difference.

This survey used anonymized patient data and was exempt from approval by an ethics committee according to the French national ethics law. Digital informed consent was obtained from all patients. A request for use of the database for research purposes was submitted to the French National Commission for Data Protection (Commission Nationale de l’Informatique et des Libertés).

Results

Demographic and general information

Among the 102,138 women and men of the targeted study sample by IPSOS, a total of 1,131 patients were recruited for the survey. Among them, 86 patients didn’t answer questions and finally 1,045 patients (355 men; 690 women) were included. The characteristics of the studied population and of the three main subgroups are described in Table 1. Among all respondents, 56 were pregnant, and 47 had not yet started ART. These 103 patients were not included in subgroups, because these subgroups were too small for being statistically analyzed. The remaining 943 patients were divided into three subgroups: people who succeeded in having a live birth following MAR (n = 522; 50%), those currently undergoing MAR treatment (n = 199; 19%), and those who dropped out of the MAR process without a live birth (n = 221; 21%). The mean time since drop out was 8.8 ± 4.9 years (95% CI: 7.7–9.9). Among this last subgroup, reasons for drop-out were reported as follows: personal decision (n = 82; 37%), discouragement by a too many failures (n = 66; 30%), taking a temporary MAR procedure break before another attempt (n = 39; 18%), financial reasons (n = 23; 10%), and medical reasons (n = 11; 5%).

Table 1. MAR burden: A French national survey.

Characteristics of the whole population of respondents (n = 1045) and of the three main subgroups of the survey population (n = 942).

	All	People still undergoing MAR	People for whom MAR led to a live birth	People who dropped out of MAR n = 221 (21%)
	n = 1045 (100%)^a	People still undergoing MAR	People for whom MAR led to a live birth
		n = 199 (19%)	n = 522 (50%)
		(B)	(C)	(D)
Age (mean, 95% CI)
All	38.11 (37.5–38.7)	32.8 (31.6–34)	39.8 (39.1–40.4)	40.7 (39.5–41.9)
Female	38.1 (n = 689) (37.4–38.8)	32.8 (n = 112) (31.4–34.2)	39.5 (n = 360) (38.7–40.3)	40.8 (n = 151) (39.3–42.3)
Male	38.2 (n = 356) (37.2–39.2)	32.9 (n = 87) (30.9–34.9)	40.4 (n = 162) (39.1–41.7)	40.5 (n = 70) (38.5–42.5)
Age groups (n, %)
18–24	42 (4.0%)	20 (10.1%) (+CD)	8 (1.5%)	6 (2.7%)
25–34	262 (25.1%)	105 (52.8%) (+CD)	87 (16.7%)	30 (13.6%)
35–44	509 (48.7%)	63 (31.7%)	301 (57.7%) (+BD)	100 (45.2%) (+B)
45–50	232 (22.2%)	11 (5.5%)	126 (24.1%) (+B)	85 (38.5%) (+BC)
Marital status (n, %)
Single	100 (9.6%)	11 (5.5%)	44 (8.4%)	31 (14%) (+BC)
In a couple	945 (90.4%)	188 (94.5%) (+D)	478 (91.6%) (+D)	190 (86.0%)
Number of children under 18 at home (n, %)
None	297 (28.4%)	78 (39.2%) (+C)	18 (3.4%)	155 (70.1%) (+BC)
1	330 (31.6%)	85 (42.7%) (+CD)	173 (33.1%) (+D)	39 (17.6%)
2	321 (30.7%)	31 (15.6%)	253 (48.5%) (+BD)	20 (9.0%)
3 or more	97 (9.3%)	5 (2.5%)	78 (15.0%) (+BD)	7 (3.2%)
Net mensual household income after deduction of income taxes (n, %)
1.250 € or less	75 (7.2%)	28 (14.1%) (+C)	22 (4.2%)	18 (8.1%) (+C)
1.251 to 2.000 €	164 (15.7%)	42 (21.1%) (+C)	62 (11.9%)	39 (17.6%) (+C)
2.001 to 3.000 €	265 (25.4%)	36 (18.1%)	148 (28.4%) (+B)	52 (23.5%)
More than 3.000 €	436 (41.7%)	76 (38.2%)	237 (45.4%)	84 (38%)
Refusal to answer	105 (10.0%)	17 (8.5%)	53 (10.2%)	28 (12.7%)

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(+B, +C, +D) p <0.05 Significant statistical superior differences between People still undergoing MAR, People for whom MAR led to a live birth and People who dropped out of MAR

^a Among all respondents who weren’t included in subgroups, 56 were pregnant, and 47 had not yet started MAR.

Among patients who were currently undergoing MAR treatment (n = 199), the procedures were distributed as follows: intrauterine insemination (IUI) with sperm from the partner (n = 99; 50%), IUI with sperm from a donor (n = 21; 10%), in vitro fertilization (n = 64; 32%), and others (n = 15; 8%). The respondents had already experienced an average of 3.6 (95% CI: 3.3–3.9) MAR attempts among the whole study sample (n = 1045) and 3.9 (95% CI: 3.4–4.4) attempts among the patients who dropped out of the MAR process (n = 221). The mean general level of self-reported well-being was 6.7 (95% CI: 6.6–6.9) out of 10 and was significantly lower in people who dropped out of MAR (6.5, 95% CI: 6.1–6.8) vs the 2 other subgroups (p< 0.05).

Personal history before resorting to a MAR procedure

The two main concerns prior to starting a MAR procedure were the risk of never becoming a parent (n = 593, 57%) and self-doubt about their own accountability in prior pregnancy failures (n = 485, 46%). Other findings are presented in Table 2. For 45% of respondents (n = 470), the first specialized consultation occurred less than 12 months after attempting natural conception. Among the population currently undergoing MAR, the patients had started their reproductive project 3.8 years (95% CI: 3.6–4.0) before participating in the survey.

Table 2. A French national survey.

MAR burden in the whole studied population (n = 1045) and in the three main subgroups of the respondents (n = 942). Responses to the question: “When you encountered first difficulties in having a child, what were all the questions you asked yourself at that time?”.

	All (%)	People still undergoing MAR n = 199 (19%)	People for whom MAR led to a live birth n = 522 (50%)	People who dropped out of ART n = 221 (21%)
	n = 1045 (100%)	People still undergoing MAR n = 199 (19%)	People for whom MAR led to a live birth n = 522 (50%)	People who dropped out of ART n = 221 (21%)
	n = 1045 (100%)	(B)	(C)	(D)
Will I ever have a child?	n = 593 (57%)	n = 90 (45%)	n = 337 (65%) (+BD)	n = 119 (54%)
Is it my fault?	n = 485 (46%)	n = 85 (43%)	n = 259 (50%)	n = 104 (47%)
Will I have to adopt?	n = 371 (36%)	n = 62 (31%)	n = 201 (38%)	n = 86 (39%)
Is it my partner’s fault?	n = 365 (35%)	n = 59 (30%)	n = 207 (40%) (+B)	n = 75 (34%)
Will I be eligible for ART?	n = 228 (22%)	n = 47 (24%)	n = 107 (20%)	n = 50 (23%)
Is it related to my lifestyle?	n = 197 (19%)	n = 39 (20%)	n = 99 (19%)	n = 40 (18%)
Is there a l history in my family or that of my partner’s?	n = 203 (19%)	n = 38 (19%)	n = 106 (20%)	n = 41 (19%)
Is it related to my weight?	n = 176 (17%)	n = 44 (22%) (+D)	n = 87 (17%)	n = 28 (13%)
Is it hereditary?	n = 168 (16%)	n = 33 (17%)	n = 83 (16%)	n = 40 (18%)
Is it related to my diet?	n = 150 (14%)	n = 41 (21%) (+C)	n = 58 (11%)	n = 35 (16%)
Is it related to my professional environment?	n = 122 (12%)	n = 26 (13%)	n = 57 (11%)	n = 19 (10%)

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(+B, +C, +D) p <0.05 Significant statistical superior differences between People still undergoing MAR, People for whom MAR led to a live birth and People who dropped out of MAR

Perceptions of and relationship with the infertility healthcare system

Overall, the level of satisfaction with the infertility healthcare system was deemed high, with an average rating of 6.9 (95% CI: 6.7–7.0) out of 10, with 20% of respondents reporting a very high level of satisfaction (≥9 out of 10). However, satisfaction with MAR depended on the outcome; the people for whom MAR succeeded (n = 522) reported an average MAR satisfaction rating of 7.8 (95% CI: 7.6–7.9), while the average satisfaction rating was 5.3 (95% CI: 4.8–5.7) for people who dropped out of MAR (n = 221) (p< 0.05). Furthermore, the vast majority of patients expressed very high satisfaction regarding medical care received (Fig 1). The only rating that was substantially below the others was about non-medical support that was proposed (such as psychologists or patient support groups). The women and men surveyed did not show any significant differences in their feelings about and experiences with MAR.

Fig 1 — Percentage of answers to the question “Would you say that you have been very, somewhat, rather not or not at all satisfied with the following as part of your MAR program?” (n = 1 045).

Among people who had experienced a MAR procedure, 63% (n = 655) were offered an investigation of infertility as soon as they consulted for difficulties in conceiving a child. For 13% of them (n = 132), the gynecologist advised them to keep trying and come back later.

The paraclinical tests before starting MAR were deemed necessary (n = 972, 93%) and useful (n = 955, 91%) by the majority of surveyed people, but 75% also considered them stressful (n = 782) and long (n = 789). People currently on the MAR process (n = 199) were also likely to find these tests confusing (n = 126, 63%) and incomprehensible (n = 94, 47%). Otherwise, a majority of respondents (n = 187, 85%) among the subgroup of patients having dropped out of MAR management (n = 221) reported that the examinations needed for controlled ovarian stimulation (COS) monitoring were burdensome or very burdensome. One-third of the respondents (n = 63, 32%) currently on MAR process (n = 199) considered them very burdensome. Concerning the treatments for COS, the majority (75%, n = 149) thought that their current treatment of ovarian stimulation by gonadotropin injection had an impact on their daily life, 32% (n = 64) felt uncomfortable with self-injections and 31% (n = 62) thought that the treatment was hard to follow.

Psychological, physical and social impact (Figs 2–5)

Fig 2 — Percentage of answers to the question “Would you say each of the following happen to you very often, often, sometimes, rarely, or never?” (n = 1 045).

Fig 5 — Percentage of answers to the question “Regarding your relationship with those around you, would you say that you felt each of the following a lot, moderately, a little, not at all?” (n = 1 045).

When responding to the question “What score between 1 and 10 would you give today to assess the psychological impact of your MAR care? (1 = you do not feel any psychological consequences and 10 means that you consider yourself to be very psychologically impacted)”, the psychological impact was the most important impact of infertility and MAR process among the different areas explored (6.2, 95% CI: 6.0–6.4) with no significative difference between the 3 subgroups but a significant higher impact for women (6.4, 95% CI: 6.2–6.7) that for men (5.9, 95% CI: 5.5–6.2) (p< 0.05).

The psychological impact was experienced strongly regardless of the situation in the MAR process (Fig 2). The majority (71%, n = 142) of the respondents currently on MAR process thought once a day or more often about their desire to have children. Among people who dropped out of MAR without a baby, 30% (n = 66) thought about their desire to have children daily at the time of the survey. The score self-reported for evaluating the physical impact of infertility and MAR was rated 5.7 (95% CI: 5.4–5.9) out of 10, and this score wasn’t significantly different between subgroups. However, physical impact was significantly increased for women: 5.8 (95% CI: 5.5–6.0) vs men 5.4 (95% CI: 5.0–5.7).

Fig 3 shows the percentage of response for each item and highlights the impact of MAR from moderate to a lot on sexual life (57%, n = 539; 93 not concerned), pain during transvaginal oocyte retrieval (55%, n = 410; 302 not concerned), intense fatigue or exhaustion (53%, n = 510; 87 not concerned), and mood disorders (52%, n = 491; 99 not concerned). Overall, 60% (n = 546; 129 not concerned) of respondents estimated they had a good ability to tolerate infertility treatments.

The self-reported impact on affective life was rated 5.7 (95% CI: 5.5–5.9) out of 10, with no significant difference between women and men (p≥ 0.05).

Different statements were tested regarding relationships within the couple (n = 945), and the results are summarized in Fig 4. Table 3 shows that impact on the couple's daily life was significantly increased in many areas for couples currently undergoing a MAR process (p < 0.05). Concerning the impact on sexual life, 21% (n = 202) of patients reported that infertility and MAR led to not having sexual intercourse for several weeks or even months. We didn’t observe any difference between women and men, with 21.1% of women and 21.8% of men who reported having no sexual intercourse for several weeks (p≥ 0.05).

Table 3. A French national survey.

	All	People still undergoing MAR	People for whom MAR led to a live birth	People that drop out of MAR n = 190 (20%)
	n = 945 (100%)	n = 188 (20%)	n = 478 (51%)	(D)
		n = 188 (20%)	(C)
		(B)	(C)
a lot + moderately^a (n, %)
Willingness to refocus on your relationship	n = 571	n = 132	n = 265	n = 111
Willingness to refocus on your relationship	60%	70% (+CD)	55%	59%
Feeling of inequality within your couple in how MAR was experienced	n = 476	n = 105	n = 227	n = 101
	50%	56% (+C)	48%	53%
A greater pleasure felt in the “little moments of daily life” with your partner	n = 475	n = 112	n = 223	n = 86
	50%	60% (+CD)	47%	45%
Absence of sexual intercourse for several weeks or even months	n = 457	n = 107	n = 218	n = 88
	48%	57% (+CD)	46%	46%
Repeated tensions for "small problems" of daily life	n = 456	n = 99	n = 223	n = 91
Repeated tensions for "small problems" of daily life	48%	53%	47%	48%
Difficulties having sex	n = 441	n = 102	n = 215	n = 86
Difficulties having sex	47%	54% (+C)	45%	45%
Feeling of injustice towards your partner	n = 431	n = 109	n = 188	n = 91
Feeling of injustice towards your partner	46%	58% (+C)	39%	48% (+C)
Irritability towards your partner	n = 432	n = 105	n = 204	n = 82
Irritability towards your partner	46%	56% (+CD)	43%	43%
Decreased desire for your partner	n = 419	n = 92	n = 199	n = 86
Decreased desire for your partner	44%	49%	42%	45%
Wanting to separate / divorce your partner	n = 271	n = 75	n = 95	n = 68
Wanting to separate / divorce your partner	29%	40% (+C)	20%	36% (+C)

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MAR burden on the affective couple’s daily—live.(B,C,D) p <0.05: Significant statistical differences between people still undergoing MAR, people for whom MAR led to a live birth and people who dropped out of MAR.

(+B, +C, +D) p <0.05 Significant statistical superior differences between People still undergoing MAR, People for whom MAR led to a live birth and People who dropped out of MAR

^aThe % displays the subtotal of people mentioning “a lot” or “moderately” at each item. The statistical differences have been calculated on this subtotal.

The average rating for the self-reported impact of MAR on relationships within social networks was 4.9 (95% CI: 4.6–5.1) out of 10 (n = 1045), with a significant higher impact (5.3, 95% CI: 4.8–5.8) or the subgroup of patients currently undergoing MAR (n = 199). When looking into the relationship with the social environment in more detail (Fig 5), the majority felt supported from moderate to a lot by friends and family (60%, n = 629), but they also often felt, from moderate to a lot, that no one was able to understand them (57%, n = 593) and developed jealousy towards pregnant women around them (52%, n = 546).

Burden of MAR on professional life (Fig 6)

To the question “What score between 1 and 10 would you give today to assess the impact of MAR on your professional life? 1 = MAR had no impact on your professional life and 10 = you feel that your professional life is very impacted”, the average rating for the self-reported impact of MAR on professional life was 4.8 (95% CI: 4.6–5.0) out of 10 with a significant higher impact (5.3, 95% CI: 4.9–5.7) for the subgroup of active worker patients currently in a MAR process compared to people for whom MAR led to a live birth (4.7, 95% CI: 4.5–4.9) and people who dropped out of MAR(4.4, 95%: 4.0–4.8) (p< 0.05). Overall professional impact was significantly increased in women (4.9, 95% IC: 4.7–5.1) compared to men (4.6, 95%: 4.3–4.9), (p< 0.05).

Among patients currently undergoing MAR (n = 199), 93% (n = 185) were active workers. Among them, 63% (n = 116) considered MAR to have had an impact on the organization of their working time, and 51% (n = 95) reported that they were less motivated to go to work because of reduced well-being at work. Of the respondents, 55% (n = 101) reported a significant increase in their level of stress at work that was induced by infertility and MAR. Thus, 49% (n = 91) of patients felt that infertility and MAR had a significant impact on the quality of their work. On the other hand, 46% (n = 86) admitted that they had to lie to justify absenteeism necessary for the MAR procedure, and only 55% (n = 101) of them dared to use the absence authorizations provided by French law for people who underwent MAR. Finally, 35% of people (n = 65) stated that they preferred to resign as opposed to devote themselves fully to their career. Only 58% of respondents (n = 108) reported that they felt that their employer was understanding. Finally, 37% of them (n = 68) declared they had been pressured by management or colleagues during their career. This accumulation of negative reactions within the company led more than 35% of respondents (n = 64) to change employers. Table 4 reports the very important and rather important professional self-reported consequences of MAR. Professional impact was significantly more important (very important + rather important) for women concerning the work organization time management (p< 0.05).

Table 4. MAR and professional burden for women and men who reported to have had a very significant and a rather significant impact on their professional life.

	All	Men	Women
	n = 984	n = 347	n = 637
	(100%)	(35%)	(65%)
		(E)	(F)
Professional consequences
n (%) Very+ rather important
The organization of your work time	n = 499	n = 160	n = 339
The organization of your work time	(51%)	(46%)	(53%) (+E)
Your stress level at work	n = 472	n = 153	n = 139
Your stress level at work	(48%)	(44%)	(50%)
Your motivation to go to work in the morning	n = 420	n = 138	n = 282
Your motivation to go to work in the morning	(43%)	(40%)	(44%)
Your well-being at work	n = 429	n = 149	n = 280
Your well-being at work	(44%)	(43%)	(44%)
Your physical / intellectual capacities to work	n = 402	n = 138	n = 264
Your physical / intellectual capacities to work	(41%)	(40%)	(41%)
Your professional project/plans	n = 395	n = 143	n = 252
Your professional project/plans	(40%)	(41%)	(40%)
Relationships with your work colleagues	n = 362	n = 130	n = 232
Relationships with your work colleagues	(37%)	(38%)	(36%)
The quality of your work	n = 351	n = 135	n = 216
The quality of your work	(36%)	(39%)	(34%)
Your evolution in terms of professional responsibilities	n = 312	n = 115	n = 197
	(32%)	(33%)	(31%)
Your evolution in terms of salary	n = 292	n = 121	n = 171
Your evolution in terms of salary	(30%)	(35%) (+F)	(27%)

Open in a new tab

(+E, +F) p <0.05 Significant superior statistical differences between Men and Women

*The % displays the subtotal of people mentioning “very important” or “rather important” at each item. The statistical differences have been calculated on this subtotal.

Discussion

Despite a universal health care for every infertile couple in France and despite a high level of satisfaction regarding French medical healthcare concerning MAR, our large national survey highlighted that both infertility and MAR treatments were associated with a major psychological burden with a negative impact throughout personal, social and professional life. Several perceived gaps were identified, thereby stressing areas for improvement.

Our findings confirmed prior research and identified precise issues deserving further investigations. The self-experience of infertility is often described by individuals and couples as a stressful condition and a heartbreaking situation, with anxiety and depressive symptoms with personal, partnership and social repercussions, that could decrease quality of life [19–24]. Infertility and ART also have marital consequences, inducing difficulties in partner communication [25] and sexual dysfunction [20,26]. In a meta-analysis, Mendoça et al. reported that lubrication, orgasm and satisfaction were mostly impaired in women [27]. In men, infertility has been reported to decrease self-esteem and sexual performance, with hypoactive sexual desire, erectile dysfunction and lack of sexual satisfaction [28,29]. In our study, 21.1% of women and 21.8% of men reported having no sexual intercourse for several weeks. Unfortunately, we haven’t enough data to differentiate dysfunction and lack of sexual satisfaction. This result deserves a further specific study focusing on sexual dysfunction. Because ART permits to obtain a baby without sexuality, medical staff should be aware of the sexual quality of life in couples during the medical process and counsel them to maintain a satisfying relationship quality. In a meta-analysis, Frederiksen et al. concluded that psychological support could reduce psychological distress and improve pregnancy rates [30]. For Hämmerli et al., psychological interventions significantly increased pregnancy rates only in couples who were not receiving medical treatment, with an RR = 1.42, 99% CI: 1.02–1.99 [31]. We hypothesize that a better relationship quality could have a direct positive effect on sexuality and on spontaneous pregnancy rates. In our survey, 34% of responders pointed out the lack of nonmedical support during their ART program.

Our work raises several issues worth considering regarding infertility and its medical management. Some studies have explored quality of life (QoL) as a comprehensive indicator for the assessment of the psychological impact of complex clinical conditions, such as infertility. Infertile women have a worse QoL than both infertile men and fertile controls [21,32]. These findings also suggest that the period preceding the result of a treatment outcome can be considered a crucial moment for worsening psychological well-being relative to the beginning of ovarian stimulation and oocyte retrieval [32]. Furthermore, social, psychological and physical dimensions of QoL seemed to be more affected after ART failure [33].

We found similar results to those presented in the literature concerning the psychosocial impact of infertility and ART management [7,19,20,24,33]. Respondents appeared to be frequently impacted in many aspects of their life. Multiple concerns were reported, and numerous negative feelings and psychological impacts were raised. People were also somehow disrupted in their social interactions, and many respondents declared physical symptoms that were probably of multifactorial origin. Noticeably, most of those problems were reported regardless of the phase at which people were within the ART process, even for people who had dropped out of ART.

Women often complain of the burden of treatment, particularly in IVF. Physicians should adopt any available strategies to increase success of ART and reduce the risk of drop -out as well as the risk of complications, interruption of ovarian stimulation, and failure, such as the use of nomograms in the definition of gonadotropins doses for ovarian stimulation [34]. In this regard, the impact of procedure failure, particularly due to failed ovarian stimulation or complication as Ovarian Hyperstimulation syndrome on the psychology and wellbeing of patients could be a further point of investigation.

While the consequences of infertility and ART on QoL, life satisfaction, marital life, sexuality and stress attitude have already been described, our study also pointed out the strong impact of ART on professional life, both on the individual working life of the respondents and on the enterprise environment. The work organization time management was a major concern, in particular for women, even in France, where the government health insurance covers the cost of absences from work for infertility treatment. To our knowledge, human resources teams have not yet embraced organizational support for decreasing the psychosocial burden of ART, which could induce depressive symptoms, anxiety, absenteeism, and job instability. It is possible that enterprise policies should be adjusted to help both women and men face ART logistics and help them combine professional and personal life during this difficult time. In France, enterprises probably underestimate that one in five people of reproductive age consult a fertility specialist at least one time in their life. Moreover, it has been reported that high-level occupational women often postpone childbearing until after age 35 and more often experience infertility related to age [35].

Our study has several strengths. First, it is a national survey including a very large number of women and men affected by infertility. Second, the fact that we included patients going through different stages of the ART process (successful ART, currently on ART and dropped-out of the ART process without a baby) allowed us to offer a global longitudinal view throughout the medical process. Third, the high number of questions, which were deeply anchored in day-to-day concerns, permitted us to retrieve concrete feedback that is thought to be directly actionable to implement countermeasures for quality of life and patient experience across the care cycle. Fourth. and in parallel with subjective insights, we collected real-life data regarding the actual management of patients at the national scale.

However, we recognize some limitations. The main limitation is that we have not used validated scales such as the FertiQol or Fertility Problem Inventory (FPI) for measuring specific patient outcomes [36]. However, validated scales are most useful for studying QoL changes in clinical interventional studies. In our study, we wanted to assess “real life” outcomes, with QoL outcomes determined from the real-life experience: patient outcomes and surveys have been determined by patients themselves (via a patient association, www.bamp.fr) and by experts following their professional experience. Our idea to build the survey was generated from the WHO definition of QoL. QoL is a wide concept for individuals, corresponding to “individuals’ perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns” [37]. Therefore, the perspective of our work was to provide valuable information to physicians about the impact of infertility and ART on QoL and to help them to better support infertile couples in their everyday lives. One other limitation of our work is that we did not have medical data about the respondents, limiting the analysis of results. Indeed, many psychosocial factors could influence well-being and mental health during the ART process. For example, we do not know the etiology of the infertility of respondents. Massaroti et al. observed that women expressed more anxiety and general distress in cases of female infertility [38].

An online survey has some inherent biases. For instance, it limits study samples to people with internet access; these respondents are likely to be slightly different from a sociological standpoint than those without internet access. However, this means of surveying people, including patients, has dramatically grown over the last decade and is now considered valid if conducted according to predefined and established methods [39]. Second, the three subgroups of patients were quite unbalanced among the whole study sample; due to this and to the observational design of the study, no definitive interpretation can be drawn from the differences measured between subgroups for some items. In particular, a causal relationship cannot be inferred with certainty between some baseline or care characteristics and subsequent outcomes. Third, the endpoints measurements were self-reported, increasing the risk of social desirability bias.

Conclusions

Our national survey of a large sample of women and men showed a high overall level of satisfaction regarding the medical care received, even though some gaps could be found, particularly regarding a lack of nonmedical support. Nevertheless, our findings confirm that the burden of infertility and MAR treatments is not negligible, particularly in sexual, psychosocial and professional life. We suggest that the internal quality control program of each Reproductive Medicine center should include the monitoring of fertility-related quality of life throughout all the MAR procedures, as is done for the live-birth rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome rate. Moreover, the QoL evaluations must consider both women and men. Reproductive Medicine centers should be encouraged to develop nonmedical support for all patients at any stage of infertility treatment. Enterprises should be warned of the professional impact of infertility to help employees reconcile personal and professional life.

Supporting information

S1 File

(DOCX)

Click here for additional data file.^{(63.9KB, docx)}

S2 File

(DOCX)

Click here for additional data file.^{(59.7KB, docx)}

Data Availability

All relevant data are within the manuscript. The anonymized MAR data set has been registered in Mendeley Data https://data.mendeley.com/datasets/6rmxbd56cf/1

Funding Statement

Financial support of the IPSOS Survey and the statistical analysis was provided by Gedeon Richter France. The funder provided support in the form of salaries for C. Solignac and E. Arbo but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder also assumed all the expenses for publication’s fees. The specific roles of these authors are articulated in the ‘author contributions’ section.

References

1.Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod. 2017;32: 1786–1801. 10.1093/humrep/dex234 [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Cunningham J. Infertility: A primer for primary care providers. JAAPA. 2017;30: 19–25. 10.1097/01.JAA.0000522130.01619.b7 [DOI] [PubMed] [Google Scholar]
3.Duron S, Slama R, Ducot B, Bohet A, Sørensen DN, Keiding N, et al. Cumulative incidence rate of medical consultation for fecundity problems—analysis of a prevalent cohort using competing risks. Hum Reprod. 2013;28: 2872–2879. 10.1093/humrep/det293 [DOI] [PubMed] [Google Scholar]
4.Roustaei Z, Räisänen S, Gissler M, Heinonen S. Fertility rates and the postponement of first births: a descriptive study with Finnish population data. BMJ Open. 2019;9: e026336 10.1136/bmjopen-2018-026336 [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Menning BE. The emotional needs of infertile couples. Fertil Steril. 1980;34: 313–319. 10.1016/s0015-0282(16)45031-4 [DOI] [PubMed] [Google Scholar]
6.Social Schmidt L. and psychological consequences of infertility and assisted reproduction—what are the research priorities? Hum Fertil (Camb). 2009;12: 14–20. 10.1080/14647270802331487 [DOI] [PubMed] [Google Scholar]
7.Lund R, Sejbaek CS, Christensen U, Schmidt L. The impact of social relations on the incidence of severe depressive symptoms among infertile women and men. Hum Reprod. 2009;24: 2810–2820. 10.1093/humrep/dep257 [DOI] [PubMed] [Google Scholar]
8.Boivin J, Takefman J, Braverman A. The fertility quality of life (FertiQoL) tool: development and general psychometric properties. Hum Reprod. 2011;26: 2084–2091. 10.1093/humrep/der171 [DOI] [PMC free article] [PubMed] [Google Scholar]
9.Koert E, Takefman J, Boivin J. Fertility quality of life tool: update on research and practice considerations. Hum Fertil (Camb). 2019; 1–13. 10.1080/14647273.2019.1648887 [DOI] [PubMed] [Google Scholar]
10.Adamson GD, de Mouzon J, Chambers GM, Zegers-Hochschild F, Mansour R, Ishihara O, et al. International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011. Fertil Steril. 2018;110: 1067–1080. 10.1016/j.fertnstert.2018.06.039 [DOI] [PubMed] [Google Scholar]
11.De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, et al. ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020: hoz038 10.1093/hropen/hoz038 [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Verhaak CM, Lintsen AME, Evers AWM, Braat DDM. Who is at risk of emotional problems and how do you know? Screening of women going for IVF treatment. Hum Reprod. 2010;25: 1234–1240. 10.1093/humrep/deq054 [DOI] [PubMed] [Google Scholar]
13.Gameiro S, Boivin J, Dancet E, de Klerk C, Emery M, Lewis-Jones C, et al. ESHRE guideline: routine psychosocial care in infertility and medically assisted reproduction-a guide for fertility staff. Hum Reprod. 2015;30: 2476–2485. 10.1093/humrep/dev177 [DOI] [PubMed] [Google Scholar]
14.Gaskins AJ, Sundaram R, Buck Louis GM, Chavarro JE. Predictors of Sexual Intercourse Frequency Among Couples Trying to Conceive. J Sex Med. 2018;15: 519–528. 10.1016/j.jsxm.2018.02.005 [DOI] [PMC free article] [PubMed] [Google Scholar]
15.Zurlo MC, Cattaneo Della Volta MF, Vallone F. Infertility-Related Stress and Psychological Health Outcomes in Infertile Couples Undergoing Medical Treatments: Testing a Multi-dimensional Model. J Clin Psychol Med Settings. 2019. 10.1007/s10880-019-09653-z [DOI] [PubMed] [Google Scholar]
16.Troude P, Guibert J, Bouyer J, de La Rochebrochard E, DAIFI Group. Medical factors associated with early IVF discontinuation. Reprod Biomed Online. 2014;28: 321–329. 10.1016/j.rbmo.2013.10.018 [DOI] [PubMed] [Google Scholar]
17.Troude P, Santin G, Guibert J, Bouyer J, de La Rochebrochard E, DAIFI Group. Seven out of 10 couples treated by IVF achieve parenthood following either treatment, natural conception or adoption. Reprod Biomed Online. 2016;33: 560–567. 10.1016/j.rbmo.2016.08.010 [DOI] [PubMed] [Google Scholar]
18.Belgherbi S, de La Rochebrochard E. Can men be trusted in population-based surveys to report couples’ medical care for infertility? BMC Med Res Methodol. 2018;18: 111 10.1186/s12874-018-0566-y [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Fassino S, Pierò A, Boggio S, Piccioni V, Garzaro L. Anxiety, depression and anger suppression in infertile couples: a controlled study. Hum Reprod. 2002;17: 2986–2994. 10.1093/humrep/17.11.2986 [DOI] [PubMed] [Google Scholar]
20.Facchin F, Somigliana E, Busnelli A, Catavorello A, Barbara G, Vercellini P. Infertility-related distress and female sexual function during assisted reproduction. Hum Reprod. 2019;34: 1065–1073. 10.1093/humrep/dez046 [DOI] [PubMed] [Google Scholar]
21.Namdar A, Naghizadeh MM, Zamani M, Yaghmaei F, Sameni MH. Quality of life and general health of infertile women. Health Qual Life Outcomes. 2017;15: 139 10.1186/s12955-017-0712-y [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Patel A, Sharma PSVN, Kumar P, Binu VS. Illness Cognitions, Anxiety, and Depression in Men and Women Undergoing Fertility Treatments: A Dyadic Approach. J Hum Reprod Sci. 2018;11: 180–189. 10.4103/jhrs.JHRS_119_17 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Galhardo A, Pinto-Gouveia J, Cunha M, Matos M. The impact of shame and self-judgment on psychopathology in infertile patients. Hum Reprod. 2011;26: 2408–2414. 10.1093/humrep/der209 [DOI] [PubMed] [Google Scholar]
24.Peterson BD, Sejbaek CS, Pirritano M, Schmidt L. Are severe depressive symptoms associated with infertility-related distress in individuals and their partners? Hum Reprod. 2014;29: 76–82. 10.1093/humrep/det412 [DOI] [PubMed] [Google Scholar]
25.Martins MV, Basto-Pereira M, Pedro J, Peterson B, Almeida V, Schmidt L, et al. Male psychological adaptation to unsuccessful medically assisted reproduction treatments: a systematic review. Hum Reprod Update. 2016;22: 466–478. 10.1093/humupd/dmw009 [DOI] [PubMed] [Google Scholar]
26.Smith NK, Madeira J, Millard HR. Sexual function and fertility quality of life in women using in vitro fertilization. J Sex Med. 2015;12: 985–993. 10.1111/jsm.12824 [DOI] [PubMed] [Google Scholar]
27.Mendonça CR de, Arruda JT, Noll M, Campoli PM de O, Amaral WN do. Sexual dysfunction in infertile women: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2017;215: 153–163. 10.1016/j.ejogrb.2017.06.013 [DOI] [PubMed] [Google Scholar]
28.Jamil S, Shoaib M, Aziz W, Ather MH. Does male factor infertility impact on self-esteem and sexual relationship? Andrologia. 2020;52: e13460 10.1111/and.13460 [DOI] [PubMed] [Google Scholar]
29.Lotti F, Maggi M. Sexual dysfunction and male infertility. Nat Rev Urol. 2018;15: 287–307. 10.1038/nrurol.2018.20 [DOI] [PubMed] [Google Scholar]
30.Frederiksen Y, Farver-Vestergaard I, Skovgård NG, Ingerslev HJ, Zachariae R. Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: a systematic review and meta-analysis. BMJ Open. 2015;5: e006592 10.1136/bmjopen-2014-006592 [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Hämmerli K, Znoj H, Barth J. The efficacy of psychological interventions for infertile patients: a meta-analysis examining mental health and pregnancy rate. Hum Reprod Update. 2009;15: 279–295. 10.1093/humupd/dmp002 [DOI] [PubMed] [Google Scholar]
32.Agostini F, Monti F, Andrei F, Paterlini M, Palomba S, La Sala GB. Assisted reproductive technology treatments and quality of life: a longitudinal study among subfertile women and men. J Assist Reprod Genet. 2017;34: 1307–1315. 10.1007/s10815-017-1000-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Milazzo A, Mnatzaganian G, Elshaug AG, Hemphill SA, Hiller JE, Astute Health Study Group. Depression and Anxiety Outcomes Associated with Failed Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis. PLoS ONE. 2016;11: e0165805 10.1371/journal.pone.0165805 [DOI] [PMC free article] [PubMed] [Google Scholar]
34.Di Paola R, Garzon S, Giuliani S, Laganà AS, Noventa M, Parissone F, et al. Are we choosing the correct FSH starting dose during controlled ovarian stimulation for intrauterine insemination cycles? Potential application of a nomogram based on woman’s age and markers of ovarian reserve. Arch Gynecol Obstet. 2018;298: 1029–1035. 10.1007/s00404-018-4906-2 [DOI] [PubMed] [Google Scholar]
35.Schmidt L, Sobotka T, Bentzen JG, Nyboe Andersen A, ESHRE Reproduction and Society Task Force. Demographic and medical consequences of the postponement of parenthood. Hum Reprod Update. 2012;18: 29–43. 10.1093/humupd/dmr040 [DOI] [PubMed] [Google Scholar]
36.Kitchen H, Aldhouse N, Trigg A, Palencia R, Mitchell S. A review of patient-reported outcome measures to assess female infertility-related quality of life. Health Qual Life Outcomes. 2017;15: 86 10.1186/s12955-017-0666-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
37.WHOQOL: measuring quality of life. [cited 25 Mar 2020]. Available: https://apps.who.int/iris/handle/10665/63482
38.Massarotti C, Gentile G, Ferreccio C, Scaruffi P, Remorgida V, Anserini P. Impact of infertility and infertility treatments on quality of life and levels of anxiety and depression in women undergoing in vitro fertilization. Gynecol Endocrinol. 2019;35: 485–489. 10.1080/09513590.2018.1540575 [DOI] [PubMed] [Google Scholar]
39.Colbert CY, Diaz-Guzman E, Myers JD, Arroliga AC. How to interpret surveys in medical research: a practical approach. Cleve Clin J Med. 2013;80: 423–435. 10.3949/ccjm.80a.12122 [DOI] [PubMed] [Google Scholar]

PLoS One. doi: 10.1371/journal.pone.0238945.r001

Decision Letter 0

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PONE-D-20-12026

The burden of assisted reproductive technologies (ART) on psychosocial and professional life: results from a French survey

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Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

This study used a sample from an online survey which included 1,045 (355 men and 690 women) living or lived the experience of infertility and ART. This data provided an opportunity to evaluate the impact on quality of live for both men and women, which is initiative in ART associated researches.

The sampling method used by the authors is sound and represents the population, which is an information rich and has power for statistical test.

The authors provided detailed demographics of patients and patients’ responses for physical and mental problems asked in the questionnaire developed for the study in tables and figures, which helps readers to understand their results.

However, the authors didn’t provide statistical test results such that no solid evidences to support their discussion and conclusion. Following I would like to provide suggestions to improve this manuscript:

line 126; Descriptive statistics include frequency tables, means and standard deviations. I suggest use 95% Confidence interval to replace ± standard error.

line 137; Among all respondents, 56 were pregnant, and 47 had not yet started ART. These 103 patients not included in subgroups, which needs to indicate.

Line 147; intrauterine insemination (IUI) with sperm from the partner (n=99; 50%), IUI with sperm from a donor (n=21; 10%), those are fertility treatment but not ART since ART refers to IVF.

Line 148; an average 3.6±4.2, better to use mean and 95% confident intervals, noticed that 3.6 – 4.2 < 0, which makes no sense.

Line 150; The authors claim “The mean general level of self-reported well-being was 6.7±1.7 out of 10 and was not significantly different among the three subgroups.” I suggest providing P value to specify statistical significance.

Table 1; suggest use 95% confident intervals replace SD for continuous variable age, suggest use P values to specify statistical significance between sub-groups

Table 2; Suggest use P values to specify statistical significance between sub-groups

Line 171; “However, satisfaction with ART depended on the outcome of the ART; the people for whom ART succeeded (n= 522) reported an average ART satisfaction rating of 7.8±1.6, while the average satisfaction rating was 5.3±2.4 for people who dropped out of ART (n=221).” I suggest a statistical test should be performed to support this claim “satisfaction with ART depended on the outcome of the ART.” Also, not all patients had ART since some patients had fertility treatment such as IUI, which is not ART.

Line 174; Furthermore, the vast majority of patients expressed very high satisfaction regarding medical care received (figure 1). Not very clear here, again, missed statistical expressions to support this claim here. Figure 1 showed that very satisfy group less than 35% for all items. Most (>50%) are in the somewhat satisfied group for all items except the last, Aids/supports proposed to accompany you during your journey, which is 46%. It seems the authors grouped very satisfy patients and somewhat satisfied patients together for their claim here, which needs to indicate.

Line 177; Among people who had experienced ART, 63% (n= 655) were offered an investigation… to line 192, all listed % and numbers can’t be found anywhere else (tables or figures), which is confusion. Suggest make tables list those items to help readers understand

Line 209; Figure 3 shows the percentage of response for each item and highlights the impact of ART on sexual life (57%, n = 539; 93 not concerned). Suggest “… the impact of ART from moderate to a lot on sexual life…” to indicate this percent (57%) is a summation of both levels of impact (moderate and a lot). Same to the rest of description of figure 3 as well as figures 4, 5, and 6.

Line 270; In men, infertility has been reported to decrease self-esteem and sexual performance, with hypoactive sexual desire, erectile dysfunction and lack of sexual satisfaction [26,27]. In our study, 21% of patients reported having no sexual intercourse for several weeks. However, authors didn’t differentiate dysfunction and lack of sexual satisfaction between men and women though they did include both groups in their study.

Suggest performing statistic tests and provide P value for differences between subgroups of study population to support authors’ claim for their founding. P value should be provided in tables.

Suggest change the title as “The burden of fertility treatments and assisted reproductive technologies (ART) on psychosocial and professional life: results from a French survey” since this study includes patients who didn’t have ART.

Reviewer #2: Thank you for asking me to review this paper which reports findings from a study of the impact of infertility and assisted reproductive technology (ART) treatment on psychosocial wellbeing and the professional lives of women and men. While this is an important area of research, I have some reservations about this paper. I have the following comments and questions.

1) It is stated in the introduction that there is little evidence about the impact of infertility and assisted conception on psychosocial wellbeing. I disagree with this and refer to the comprehensive evidence presented in the ESHRE guidelines for psychosocial care in infertility and assisted conception:

Gameiro, S., Boivin, J., Dancet, E., de Klerk, C., Emery, M., Lewis-Jones, C., . . . Vermeulen, N. (2015). ESHRE guideline: routine psychosocial care in infertility and medically assisted reproduction - a guide for fertility staff. Human Reproduction, 30(11), pp. 2476-2485. doi:10.1093/humrep/dev177

2) In light of the evidence and the implications for practice presented in these guidelines I would argue that the current study only makes a very modest contribution to existing evidence.

3) We need some additional contextual information in the introduction to help readers. Who can have ART in France? What does it cost? Is it subsidised by government? Are there restrictions on how many cycles people can have?

4) It is stated that this was a 56 -item survey and the broad areas it covered are mentioned. I think much more information is needed about what the questions were based on (clinical experience? Existing literature?), if the questions had fixed choice response alternatives or if people gave their own responses. We also need an explanation for how satisfaction with the ‘ART health care system’ was measured. Was this one question or were respondents asked to state their satisfaction with different aspects of care? The methods section needs to detail what questions were asked and how responses were recorded.

5) The methods section should have a sub-section ‘Data management and analyses’ where the authors describe how data were grouped and analysed.

6) Were responses to questions (e.g. ‘When you first encountered difficulties in having a child, what were the questions that you asked yourself at that time?’) what the respondents answered or were they asked to choose from a list of response options? If they were fixed response options, how did the authors know that these were relevant? Were respondents given an ‘other’ option where they could say what questions they had asked themselves if they were not covered in the fixed response options?

7) The data are simply presented as frequency distributions. This makes the paper seem undigested. To understand what the data mean we at least need some statistical analyses to tell us if differences between groups are statistically significant and some univariate measures of association. Also, I think comparing women and men and reporting if they differ significantly in their responses would enhance the presentation of the data.

8) Relating to my previous point, for some of the data it is difficult to understand the rationale for presenting it by subgroup. What are readers supposed to make of the data in Table 2 for example? What does it mean if the proportions of people in the three subgroups differed in their choices of responses?

9) It is stated that the mean time since ‘drop-out’ was 8.5 years. What was the range? I presume this means that some had only recently ended treatment and others may have ended treatment more than a decade ago. It would be interesting to know if those who had ended treatment more recently differed in their responses from those who had moved on with their lives since ending treatment? After this the proportions stating various reasons for discontinuing treatment are reported. The percentages given look like proportions of the whole study sample? If so, this should be changed to proportions of those who had discontinued treatment without having had a baby.

Reviewer #3: The burden of ART is very well known since years.

However, in my opinion, studies analyzing the topic are always welcome to remember the clinical staff this important aspect of infertility.

The present study is very well done and simple to read. My decision is therefore to accept it despite the limitations underlined by the Authors.

Just few comments.

The impact of infertility on sexuality is described all the times and we know that it is present in the majority of couples. It is not difficult to understand why! My question is : there is any evidence that specific physiological approaches may avoid or solve this problem? Dealing with infertility couples since 35 years, my feeling is that it is very difficult to do it!

What it is instead terrible and requiring “ social” solutions is the impact on the professional organization. If I’m not wrong ,French is one of the few countries that formally declared infertility a social disease. Despite that, 35% of responders had to change employers. Can we image what happens in most of the other countries??

I believe that this part is the most interesting of the study and should be more analyzed in-depth because, otherwise from other psychological aspects, it is a negative impact that has to be solved by social interventions . And it is urgent to do it! It is very difficult to accept today that women, already facing all the phycological and physical impact related to infertility and ART, have to sacrifice the job and the career!

Reviewer #4: I was pleased to revise the manuscript entitled “The burden of assisted reproductive technologies (ART) on psychosocial and professional life: results from a French survey” (Manuscript Number: PONE-D-20-12026).

I was particularly pleased to review this paper. In my honest opinion, the topic is interesting enough to attract the readers’ attention. Methodology is accurate and conclusions are supported by the data analysis. Nevertheless, authors should clarify some point and improve the discussion citing relevant and novel key articles about the topic.

In general, the Manuscript may benefit from several minor revisions, as suggested below:

• All the text needs a minor language revision by a native English speaker person, in order to some typos, and grammatical errors.

• In the results it is unclear the response rate. I would suggest providing the actual number of patients who received the survey and patients who answered.

• I would suggest improving the discussion, at least briefly, highlighting the importance to adopt any available strategies to increase success of ART and reduce the risk of complications, interruption of ovarian stimulation, and failure, such as the use of nomograms in the definition of gonadotropins doses for ovarian stimulation (PMID: 30242498; PMID: 27835829) In this regard, the impact of procedure failure, particularly due to failed ovarian stimulation or complication, on the phycology of patient could be a further point of investigation.

• Regarding assisted reproductive techniques and psychological support, I would suggest discussing, at least briefly, to highlight its further importance when assisted reproductive techniques are adopt in the field of fertility preservation in oncological patients. (PMID: 32419847)

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Reviewer #1: No

Reviewer #2: Yes: Karin Hammarberg

Reviewer #3: Yes: Anna Pia Ferraretti MD, PhD

Reviewer #4: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Sep 24;15(9):e0238945. doi: 10.1371/journal.pone.0238945.r002

Author response to Decision Letter 0

22 Jul 2020

Journal requirements

1.We attest that our manuscript meets PLOS ONE's style requirements.

2. We included the questionnaire used in the study both in French and in English and we attest that it is not under a copyright (Please see the supplementary Supporting Information files)

3. Our data are available without ethical or legal restrictions, and as requested, we uploaded our anonymized data set on Mendeley data. The anonymized dataset has been registered under Courbiere Blandine (2020), “AMR dataset”, Mendeley data, V1, https://data.mendeley.com/datasets/6rmxbd56cf/1

4. Sorry for haven’t being accurate enough concerning the Funding Statement.

Financial support of the IPSOS Survey and the statistical analysis was provided by Gedeon Richter France. The funder provided support in the form of salaries for C. Solignac and E. Arbo but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder also assumed all the expenses for publication’s fees.The commercial affiliation with Gedeon Richter France doesn’t alter adherence of co-authors to PLOS ONE policies on sharing data and materials.

Specific roles of authors are better described in the ‘author contributions section:

- Pr B. Courbiere (BC) participated in the study design, questionnaire conception (56 items), data analysis, and manuscript preparation

- Dr A. Lacan (AL) participated in the data analysis and manuscript preparation

- Pr M. Grynberg (MG) participated in the study design, questionnaire conception and data analysis.

- Pr A. Grelat (AG) participated in the study design, questionnaire conception and data analysis.

- Dr C. Solignac (CS) participated in the study design, data analysis, decision to publish and preparation of the manuscript.

- Dr E. Arbo (EA) participated in the study design, data analysis, decision to publish

BC and CS were leading for writing the manuscript and dealing with reviewer comments.

All authors belang to the scientific committee group and contributed equally to the survey, by drafting key questions of the questionnaire and synthesizing results.AL and VR report no conflict of interest. BC and MG reports consulting fees and speaker’s fees from Gedeon Richter France. AG reports consulting fees from Gedeon Richter France.

The commercial affiliation with Gedeon Richter France doesn’t alter adherence of co-authors to PLOS ONE policies on sharing data and materials.

5. Concerning Competing interests:

Dr Anne Grela MD, isn’t employed by Clinique Pasteur, Centre Mistral. “Clinique Mistral” is just the name of the ART Center where she practices as a private physician

AL and VR report no conflict of interest. BC and MG reports consulting fees and speaker’s fees from Gedeon Richter France. AG reports consulting fees from Gedeon Richter France. Gedeon Richter provided salaries for C. Solignac and E. Arbo. The commercial affiliation with Gedeon Richter France doesn’t alter adherence of co-authors to PLOS ONE policies on sharing data and materials.

No authors have any competing interests that could be perceived to bias this work.

Responses to Reviewers

Reviewer #1: The manuscript “The burden of assisted reproductive technologies (ART) on psychosocial and professional life: results from a French survey” addressed impacts of infertility and assisted reproductive technologies (ART) throughout all aspects of life among infertile women and men, which is very interesting topic and rarely addressed before. This study used a sample from an online survey which included 1,045 (355 men and 690 women) living or lived the experience of infertility and ART. This data provided an opportunity to evaluate the impact on quality of live for both men and women, which is initiative in ART associated researches. The sampling method used by the authors is sound and represents the population, which is an information rich and has power for statistical test. The authors provided detailed demographics of patients and patients’ responses for physical and mental problems asked in the questionnaire developed for the study in tables and figures, which helps readers to understand their results.However, the authors didn’t provide statistical test results such that no solid evidences to support their discussion and conclusion. Following I would like to provide suggestions to improve this manuscript:

We are very grateful for the time you took to review our article and we thank you very much for your constructives commentaries that helped us to improve our manuscript.

All statistical analyses were performed with the COSI software for statistical data analysis. Now, descriptive statistical data include frequency tables, means and 95% Confidence Intervals.The description of data management and statistical analysis have been updated in the revised version of the manuscript.

> line 126; Descriptive statistics include frequency tables, means and standard deviations. I suggest use 95% Confidence interval to replace ± standard error.

Statistical analysis has been rigorously checked by a statistician, and as suggested, we updated the data in the text and in tables .

> line 137; Among all respondents, 56 were pregnant, and 47 had not yet started ART. These 103 patients not included in subgroups, which needs to indicate.

These two subgroups were too small for being analyzed as separate subgroups. This is indicated in legends of table and is now indicated in the manuscript.

> Line 147; intrauterine insemination (IUI) with sperm from the partner (n=99; 50%), IUI with sperm from a donor (n=21; 10%), those are fertility treatment but not ART since ART refers to IVF.

According to the French legislation, IUI is considered as an ART technique, as well as IVF and is submitted to the same (strict) reglementation. Only ovulation induction is considered as a “simple” fertility treatment.

Medically Assisted Reproduction (MAR) is defined by The international Glossary on Infertility and Fertility care (Zegers-Hochschild et al., 2017) and include “ovulation induction, ovarian stimulation, ovulation triggering, all ART procedures, uterine transplantation and intra-uterine, intracervical, and intravaginal insemination with semen of husband/partner or donor. In consequence, following your commentary and because we hope that our article will be read by international readers, we modified, as suggested, the title of our manuscript: instead of “The burden of fertility treatments and assisted reproductive technologies (ART) on psychosocial and professional life: results from a French survey”, we propose “The burden of Medically Assisted Reproduction (MAR) on psychosocial and professional life: results from a French survey”.

The term ART has been withdrawn in the hole manuscript and has been replaced by MAR;

> Line 148; an average 3.6±4.2, better to use mean and 95% confident intervals, noticed that 3.6 – 4.2 < 0, which makes no sense.

Standard error was replaced by 95% Confidence interval , as well as all the levels of satisfaction reported in the survey.For this result, we replaced 3.6 +/- 44.2 by 3.6 (95% CI: 3.3 to 3.9)

> Line 150; The authors claim “The mean general level of self-reported well-being was 6.7±1.7 out of 10 and was not significantly different among the three subgroups.” I suggest providing P value to specify statistical significance.

We revised all the manuscripts and added P values when the result was significant.

> Table 1; suggest use 95% confident intervals replace SD for continuous variable age, suggest use P values to specify statistical significance between sub-groups

As suggested, we replaced SD by 95% confident intervals and added P values between sub-groups when the difference was significant.

> Table 2; Suggest use P values to specify statistical significance between sub-groups

A p value<0.05 was considered as significant. Adding P values between sub-groups was difficult for the readability of the tables. For a better readability, a system of letters has been implemented in tables to illustrate the statistical differences between the subgroups. Letter B stands for people still undergoing MAR, letter C stands for people for whom MAR led to a live birth, letter D stands for People who dropped out of MAR, letter E stands for men and letter F stands for women. “+” refers to a superior significant difference. We hope that we presented the results easier to understand.

> Line 171; “However, satisfaction with ART depended on the outcome of the ART; the people for whom ART succeeded (n= 522) reported an average ART satisfaction rating of 7.8±1.6, while the average satisfaction rating was 5.3±2.4 for people who dropped out of ART (n=221).” I suggest a statistical test should be performed to support this claim “satisfaction with ART depended on the outcome of the ART.” Also, not all patients had ART since some patients had fertility treatment such as IUI, which is not ART.

As suggested, we added P values between sub-groups when results were significant. The term ART has been withdrawn from all the manuscript and has been replaced by the term Medically Assisted Reproduction (MAR), that defines better the sample of responders of our survey.

> Line 174; Furthermore, the vast majority of patients expressed very high satisfaction regarding medical care received (figure 1). Not very clear here, again, missed statistical expressions to support this claim here. Figure 1 showed that very satisfy group less than 35% for all items. Most (>50%) are in the somewhat satisfied group for all items except the last, Aids/supports proposed to accompany you during your journey, which is 46%. It seems the authors grouped very satisfy patients and somewhat satisfied patients together for their claim here, which needs to indicate.

Sorry for haven’t being accurate enough. Indeed, for statistical analysis, we grouped very satisfied patients and somewhat satisfied patients together. It is now indicated in the text.

The description of data management and statistical analysis have been updated in the revised version of the manuscript.

> Line 177; Among people who had experienced ART, 63% (n= 655) were offered an investigation… to line 192, all listed % and numbers can’t be found anywhere else (tables or figures), which is confusion. Suggest make tables list those items to help readers understand

Because our survey scanned 56 aspects of a patient's daily lives, we chose to select the most relevant results to reflect the MAR burden on psychosocial and professional life. Some results that we evaluated as of greater interest are detailed in the tables or figures, others are just mentioned in the text. However, all the anonymized data are yet available in a supporting information file.

> Line 209; Figure 3 shows the percentage of response for each item and highlights the impact of ART on sexual life (57%, n = 539; 93 not concerned). Suggest “… the impact of ART from moderate to a lot on sexual life…” to indicate this percent (57%) is a summation of both levels of impact (moderate and a lot). Same to the rest of description of figure 3 as well as figures 4, 5, and 6.

Sorry for not being accurate enough. Indeed, for statistical analysis, we grouped “a lot and moderately “patients together. It is now indicated in the text for all the descriptions of figures.

> Line 270; In men, infertility has been reported to decrease self-esteem and sexual performance, with hypoactive sexual desire, erectile dysfunction and lack of sexual satisfaction [26,27]. In our study, 21% of patients reported having no sexual intercourse for several weeks. However, authors didn’t differentiate dysfunction and lack of sexual satisfaction between men and women though they did include both groups in their study.

We agree with you that it would have been interesting to assay the reasons why so many patients reported having no sexual intercourse for several weeks/months. We added your comment in the manuscript. We added also that we didn’t observe any difference between women and men concerning sexual burden. However, focusing on the sexual impact of MAR wasn’t the primary outcome of our survey.

Our study aimed to assess all the impacts of MAR on the personal, social and professional aspects of life. It was “a real-life study” with the objective to identify gaps for improving care of infertile patients. One of the frustrating limits of our study is to have observed some gaps, but we can’t explain them. All interesting data identified in this study must be studied in the future by specific studies focused on a specific area (sexual impact, professional impact..).

> Suggest performing statistical tests and provide P value for differences between subgroups of study population to support authors’ claim for their founding. P value should be provided in tables.

We added the results of the statistical analysis in the tables. Statistical analysis has been entirely revised and methodology is better described in a specific subsection.

> Suggest change the title as “The burden of fertility treatments and assisted reproductive technologies (ART) on psychosocial and professional life: results from a French survey” since this study includes patients who didn’t have ART.

We really apologize for the misemployment of the term ART. Instead, we should have employed the term Medically Assisted Reproduction (MAR), defined by The international Glossary on Infertility and Fertility care (2017) that include “ovulation induction, ovarian stimulation, ovulation triggering, all ART procedures, uterine transplantation and intra-uterine, intracervical, and intravaginal insemination with semen of husband/partner or donor.

The term ART has been withdrawn from all the manuscript and has been replaced by MAR

Following your commentary, we changed the title of our article.

to: “The burden of Medically Assisted Reproduction (MAR) on psychosocial and professional life: results from a French survey”. We hope that you will be in agreement with this new title.

Thank you very much for your interest in our article and for the time you spent on doing interesting comments, that helped us improve our manuscript.

We added this major reference in the introduction. However, despite ESHRE guidelines concerning psychosocial care in infertility and medically assisted reproduction, our survey showed that psychosocial care is still insufficient or not adapted for a large part of infertile people. We agree with you that psychosocial care can reduce stress about medical procedures and improve lifestyle. However, in real life, physicians specialized in reproductive medicine often haven’t sufficient available tools for offering personalized and adapted psychosocial care to patients involved in an ART process.

2) In light of the evidence and the implications for practice presented in these guidelines I would argue that the current study only makes a very modest contribution to existing evidence.

With this survey, we chose to explore all the impacts of MAR on personal, social and professional life. We agree that some of our results are already known, as the impact on sexual life and psychosocial life. However, we identified a strong impact on the professional life that represents a gap still not known by employers and companies. As suggested by your colleague (Reviewer 3), we added some data in our results showing differences between women and men that need to be further studied.

3) We need some additional contextual information in the introduction to help readers. Who can have ART in France? What does it cost? Is it subsidised by the government? Are there restrictions on how many cycles people can have?

In our introduction, we added contextual information about the conditions of reimbursement of infertility treatments by the French Health System:

Despite this universal health care for every infertile French couple, the burden of medical procedures are high.

Our objective was to provide an overview about the impact of infertility and MAR process throughout the daily-life of patients. Questions were elaborated by a scientific committee composed by physicians specialized in reproductive medicine, an Economic Doctor specialized in Human Resources and wellbeing at work, and representatives from a National Infertility Association (bAMP) highly involved in France for supporting infertile couples. Before the survey, the questions were validated by infertile patients themself.

Questions were constructed both on existing literature (to validate data already described, as psychosocial impact) and on clinical experience reported both by physician and patients (as the professional impact, often described by patients).

The questions had fixed choice response alternatives. The survey was completed and submitted online. The overall well-being score was self-reported by a numeric scale with rates ranging from 0 to 10 (0 for very low well-being to 10 for very high well-being); the impact of MAR on different domains of life was evaluated from 0 to 10 (0 for very low impact to 10 for very high impact).

We included the questionnaire used in the study both in French and in English (Please see the supplementary Supporting Information file)

> 5) The methods section should have a sub-section ‘Data management and analyses’ where the authors describe how data were grouped and analysed.

Sorry for haven’t being accurate enough and a specific sub-section concerning Data management and analyses have been added.

Statistical analyses and tests were performed using COSI software (M.L.I., 1994, France). Descriptive statistics include frequency tables, mean, standard deviations and 95% confidence interval (95% CI). A p value<0.05 was considered as significant for this statistical analysis. The current article focuses on highlighting the statistical differences between specific groups of population: people still undergoing MAR, people for whom MAR led to a live birth, people who dropped out of MAR, men and women. A system of letters has been implemented in Tables to illustrate the statistical differences between these subgroups. Letter B stands for people still undergoing MAR, letter C stands for people for whom MAR led to a live birth, letter D stands for People who dropped out of MAR, letter E stands for men and letter F stands for women. “+” refers to a superior significant difference.

> 6) Were responses to questions (e.g. ‘When you first encountered difficulties in having a child, what were the questions that you asked yourself at that time?’) what the respondents answered or were they asked to choose from a list of response options? If they were fixed response options, how did the authors know that these were relevant? Were respondents given an ‘other’ option where they could say what questions they had asked themselves if they were not covered in the fixed response options?

Following your commentaries, the questions are available. We included the questionnaire used in the study both in French and in English (Please see the supplementary Supporting Information file)

> 7) The data are simply presented as frequency distributions. This makes the paper seem undigested. To understand what the data mean we at least need some statistical analyses to tell us if differences between groups are statistically significant and some univariate measures of association. Also, I think comparing women and men and reporting if they differ significantly in their responses would enhance the presentation of the data.

Statistical analysis has been rigorously checked by a statistician, and we updated the data in the text and in tables, as suggested.The description of data management and statistical analysis have been updated in the new version of the manuscript.

Moreover, we added comparisons between women and men when results were significantly different.

> 8) Relating to my previous point, for some of the data it is difficult to understand the rationale for presenting it by subgroup. What are readers supposed to make of the data in Table 2 for example? What does it mean if the proportions of people in the three subgroups differed in their choices of responses?

The current article focuses on highlighting the statistical differences between specific groups of population: people still undergoing MAR, people for whom MAR led to a live birth, people who dropped out of MAR, men and women. In table 2, a system of letters has been implemented to illustrate the statistical differences between these subgroups. Letter B stands for people still undergoing MAR, letter C stands for people for whom MAR led to a live birth, letter D stands for People who dropped out of MAR, letter E stands for men and letter F stands for women. “+” refers to a superior significant difference.A p value<0.05 was considered as significant for this statistical analysis.

> 9) It is stated that the mean time since ‘drop-out’ was 8.5 years. What was the range? I presume this means that some had only recently ended treatment and others may have ended treatment more than a decade ago. It would be interesting to know if those who had ended treatment more recently differed in their responses from those who had moved on with their lives since ending treatment? After this the proportions stating various reasons for discontinuing treatment are reported. The percentages given look like proportions of the whole study sample? If so, this should be changed to proportions of those who had discontinued treatment without having had a baby.

The mean time since drop out was 8.8 +/- 4.9 years.

We agree that it would be interesting to study if the time since ended treatment has an influence on the responses. However, analysing different subgroups in a sub-group of 221 patients would lack power for having significant results. For your information, please find below the details of these sub-groups. A specific study could further be of interest to assay the impact of infertility with the time in a population who dropped-out from medical procedures.

For each subtitle, we describe if the percentages are given from people of the whole study sample or if they are given from patients issued from a specific subgroup.

Time from MAR drop-out All (%) n=221 (100%)

2 years or less : n= 33 (14.9%)

Between 3 and 7 yrs : n= 72 (32.6%)

Between 8 and 12 yrs: n= 58 (26.2%)

Between 13 and 18 yrs: n = 39 (17.6%)

More than 18 yrs n=19 (8.6%)

Reviewer #3: The burden of ART is very well known since years. However, in my opinion, studies analyzing the topic are always welcome to remember the clinical staff this important aspect of infertility. The present study is very well done and simple to read. My decision is therefore to accept it despite the limitations underlined by the Authors.

Thank you very much for the time you spent for reviewing our manuscript. We agree with you that it is important to remember the clinical staff the important burden of infertility and MAR. In 2015, in the ESHRE guideline, Gameiro et al. reported international recommendations for providing routine psychosocial care in infertility and medically assisted reproduction. However, in real life, physicians specialized in reproductive medicine often haven’t sufficient available tools for offering personalized and adapted psychosocial care to patients involved in an ART process.

In France, despite an universal health care for every infertile couple, we observed that both infertility and MAR treatments were still associated with a major psychological burden with a negative impact throughout personal, social and professional life.

Just few comments.

> The impact of infertility on sexuality is described all the times and we know that it is present in the majority of couples. It is not difficult to understand why! My question is : there is any evidence that specific physiological approaches may avoid or solve this problem? Dealing with infertility couples since 35 years, my feeling is that it is very difficult to do it!

We agree with you that a lot of articles reported observations about the impact of infertility on sexuality. Despite guidelines for improving care in ART, we need interventional studies to study if some specific interventions could be useful for improving wellbeing and sexuality in couples during the stressful experience of infertility and MAR.In a meta-analysis, Frederiksen et al. concluded that psychological support could reduce psychological distress and improve pregnancy rates.

> What it is instead terrible and requiring “ social” solutions is the impact on the professional organization. If I’m not wrong ,French is one of the few countries that formally declared infertility a social disease. Despite that, 35% of responders had to change employers. Can we imagine what happens in most of the other countries??

In the introduction, we added contextual information about the conditions of reimbursement of infertility treatments by the French Health System. As you, we have been really surprised by these results. In France, the cost of absences from work for infertility treatment is covered by the government. Despite that, a lot of patients are shamed and don’t dare to tell it to their employers. To our knowledge, few is published about the professional impact of ART. Enterprises should be warned to help their employees reconcile personal and professional life.

> I believe that this part is the most interesting of the study and should be more analyzed in-depth because, otherwise from other psychological aspects, it is a negative impact that has to be solved by social interventions . And it is urgent to do it! It is very difficult to accept today that women, already facing all the phycological and physical impact related to infertility and ART, have to sacrifice the job and the career!

As suggested, we have developed the section about the professional impact of infertility treatments and added the table 4, comparing women and men.

I was particularly pleased to review this paper. In my honest opinion, the topic is interesting enough to attract the readers’ attention. Methodology is accurate and conclusions are supported by the data analysis. Nevertheless, authors should clarify some points and improve the discussion citing relevant and novel key articles about the topic.

Thank you very much for your interest for this article and for the time you spent reviewing it.

In general, the Manuscript may benefit from several minor revisions, as suggested below:

• All the text needs a minor language revision by a native English speaker person, in order to some typos, and grammatical errors.

All the manuscript has been revised by an native English Speaker. Please find attached the American Journal Expert Certificate.

• In the results it is unclear the response rate. I would suggest providing the actual number of patients who received the survey and patients who answered.

We added these data in the Results section.

Among the 102 138 women and men between 18 and 50 years old of the targeted study sample by IPSOS (= the largest French company in market and public opinion research), a total of 1 131 patients were recruited for the survey. Among them, 86 patients didn’t answer questions and finally 1 045 patients (355 men; 690 women) were included.

• I would suggest improving the discussion, at least briefly, highlighting the importance to adopt any available strategies to increase success of ART and reduce the risk of complications, interruption of ovarian stimulation, and failure, such as the use of nomograms in the definition of gonadotropins doses for ovarian stimulation (PMID: 30242498; PMID: 27835829) In this regard, the impact of procedure failure, particularly due to failed ovarian stimulation or complication, on the psychology of patient could be a further point of investigation.

As suggested, we added this point in the discussion.

Women often complain of the burden of treatment, particularly in IVF. Physicians should adopt any available strategies to increase success of ART and reduce the risk of drop -out as well as the risk of complications, interruption of ovarian stimulation, and failure, such as the use of nomograms in the definition of gonadotropins doses for ovarian stimulation (Di Paola et al., 2018) In this regard, the impact of procedure failure, particularly due to failed ovarian stimulation or complication as Ovarian Hyperstimulation syndrome on the psychology and wellbeing of patients could be a further point of investigation.

> • Regarding assisted reproductive techniques and psychological support, I would suggest discussing, at least briefly, to highlight its further importance when assisted reproductive techniques are adopt in the field of fertility preservation in oncological patients. (PMID: 32419847)

This article about the integrated gynaecological and psychological approach for the Fertility preservation in women affected by gynaecological cancer is very interesting. However, because we included in our survey only patients who underwent ART for infertility and not for fertility preservation, we are afraid to be out of scope in the discussion if we would add this reference. In case of fertility preservation for cancer, psychosocial impact is probably due more to the cancer itself than to the ovarian stimulation process, even if the FP procedure should be carefully performed to minimize burden in a high stressful context.

PLoS One. doi: 10.1371/journal.pone.0238945.r003

Decision Letter 1

Antonio Simone Laganà

27 Aug 2020

Psychosocial and professional burden of Medically Assisted Reproduction (MAR): results from a French survey

PONE-D-20-12026R1

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PLoS One. doi: 10.1371/journal.pone.0238945.r004

Acceptance letter

Antonio Simone Laganà

14 Sep 2020

PONE-D-20-12026R1

Psychosocial and professional burden of Medically Assisted Reproduction (MAR): results from a French survey

Dear Dr. COURBIERE:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

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(DOCX)

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Data Availability Statement

All relevant data are within the manuscript. The anonymized MAR data set has been registered in Mendeley Data https://data.mendeley.com/datasets/6rmxbd56cf/1

[pone.0238945.ref001] 1.Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod. 2017;32: 1786–1801. 10.1093/humrep/dex234 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref002] 2.Cunningham J. Infertility: A primer for primary care providers. JAAPA. 2017;30: 19–25. 10.1097/01.JAA.0000522130.01619.b7 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref003] 3.Duron S, Slama R, Ducot B, Bohet A, Sørensen DN, Keiding N, et al. Cumulative incidence rate of medical consultation for fecundity problems—analysis of a prevalent cohort using competing risks. Hum Reprod. 2013;28: 2872–2879. 10.1093/humrep/det293 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref004] 4.Roustaei Z, Räisänen S, Gissler M, Heinonen S. Fertility rates and the postponement of first births: a descriptive study with Finnish population data. BMJ Open. 2019;9: e026336 10.1136/bmjopen-2018-026336 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref005] 5.Menning BE. The emotional needs of infertile couples. Fertil Steril. 1980;34: 313–319. 10.1016/s0015-0282(16)45031-4 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref006] 6.Social Schmidt L. and psychological consequences of infertility and assisted reproduction—what are the research priorities? Hum Fertil (Camb). 2009;12: 14–20. 10.1080/14647270802331487 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref007] 7.Lund R, Sejbaek CS, Christensen U, Schmidt L. The impact of social relations on the incidence of severe depressive symptoms among infertile women and men. Hum Reprod. 2009;24: 2810–2820. 10.1093/humrep/dep257 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref008] 8.Boivin J, Takefman J, Braverman A. The fertility quality of life (FertiQoL) tool: development and general psychometric properties. Hum Reprod. 2011;26: 2084–2091. 10.1093/humrep/der171 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref009] 9.Koert E, Takefman J, Boivin J. Fertility quality of life tool: update on research and practice considerations. Hum Fertil (Camb). 2019; 1–13. 10.1080/14647273.2019.1648887 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref010] 10.Adamson GD, de Mouzon J, Chambers GM, Zegers-Hochschild F, Mansour R, Ishihara O, et al. International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011. Fertil Steril. 2018;110: 1067–1080. 10.1016/j.fertnstert.2018.06.039 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref011] 11.De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, et al. ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020: hoz038 10.1093/hropen/hoz038 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref012] 12.Verhaak CM, Lintsen AME, Evers AWM, Braat DDM. Who is at risk of emotional problems and how do you know? Screening of women going for IVF treatment. Hum Reprod. 2010;25: 1234–1240. 10.1093/humrep/deq054 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref013] 13.Gameiro S, Boivin J, Dancet E, de Klerk C, Emery M, Lewis-Jones C, et al. ESHRE guideline: routine psychosocial care in infertility and medically assisted reproduction-a guide for fertility staff. Hum Reprod. 2015;30: 2476–2485. 10.1093/humrep/dev177 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref014] 14.Gaskins AJ, Sundaram R, Buck Louis GM, Chavarro JE. Predictors of Sexual Intercourse Frequency Among Couples Trying to Conceive. J Sex Med. 2018;15: 519–528. 10.1016/j.jsxm.2018.02.005 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref015] 15.Zurlo MC, Cattaneo Della Volta MF, Vallone F. Infertility-Related Stress and Psychological Health Outcomes in Infertile Couples Undergoing Medical Treatments: Testing a Multi-dimensional Model. J Clin Psychol Med Settings. 2019. 10.1007/s10880-019-09653-z [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref016] 16.Troude P, Guibert J, Bouyer J, de La Rochebrochard E, DAIFI Group. Medical factors associated with early IVF discontinuation. Reprod Biomed Online. 2014;28: 321–329. 10.1016/j.rbmo.2013.10.018 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref017] 17.Troude P, Santin G, Guibert J, Bouyer J, de La Rochebrochard E, DAIFI Group. Seven out of 10 couples treated by IVF achieve parenthood following either treatment, natural conception or adoption. Reprod Biomed Online. 2016;33: 560–567. 10.1016/j.rbmo.2016.08.010 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref018] 18.Belgherbi S, de La Rochebrochard E. Can men be trusted in population-based surveys to report couples’ medical care for infertility? BMC Med Res Methodol. 2018;18: 111 10.1186/s12874-018-0566-y [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref019] 19.Fassino S, Pierò A, Boggio S, Piccioni V, Garzaro L. Anxiety, depression and anger suppression in infertile couples: a controlled study. Hum Reprod. 2002;17: 2986–2994. 10.1093/humrep/17.11.2986 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref020] 20.Facchin F, Somigliana E, Busnelli A, Catavorello A, Barbara G, Vercellini P. Infertility-related distress and female sexual function during assisted reproduction. Hum Reprod. 2019;34: 1065–1073. 10.1093/humrep/dez046 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref021] 21.Namdar A, Naghizadeh MM, Zamani M, Yaghmaei F, Sameni MH. Quality of life and general health of infertile women. Health Qual Life Outcomes. 2017;15: 139 10.1186/s12955-017-0712-y [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref022] 22.Patel A, Sharma PSVN, Kumar P, Binu VS. Illness Cognitions, Anxiety, and Depression in Men and Women Undergoing Fertility Treatments: A Dyadic Approach. J Hum Reprod Sci. 2018;11: 180–189. 10.4103/jhrs.JHRS_119_17 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref023] 23.Galhardo A, Pinto-Gouveia J, Cunha M, Matos M. The impact of shame and self-judgment on psychopathology in infertile patients. Hum Reprod. 2011;26: 2408–2414. 10.1093/humrep/der209 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref024] 24.Peterson BD, Sejbaek CS, Pirritano M, Schmidt L. Are severe depressive symptoms associated with infertility-related distress in individuals and their partners? Hum Reprod. 2014;29: 76–82. 10.1093/humrep/det412 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref025] 25.Martins MV, Basto-Pereira M, Pedro J, Peterson B, Almeida V, Schmidt L, et al. Male psychological adaptation to unsuccessful medically assisted reproduction treatments: a systematic review. Hum Reprod Update. 2016;22: 466–478. 10.1093/humupd/dmw009 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref026] 26.Smith NK, Madeira J, Millard HR. Sexual function and fertility quality of life in women using in vitro fertilization. J Sex Med. 2015;12: 985–993. 10.1111/jsm.12824 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref027] 27.Mendonça CR de, Arruda JT, Noll M, Campoli PM de O, Amaral WN do. Sexual dysfunction in infertile women: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2017;215: 153–163. 10.1016/j.ejogrb.2017.06.013 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref028] 28.Jamil S, Shoaib M, Aziz W, Ather MH. Does male factor infertility impact on self-esteem and sexual relationship? Andrologia. 2020;52: e13460 10.1111/and.13460 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref029] 29.Lotti F, Maggi M. Sexual dysfunction and male infertility. Nat Rev Urol. 2018;15: 287–307. 10.1038/nrurol.2018.20 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref030] 30.Frederiksen Y, Farver-Vestergaard I, Skovgård NG, Ingerslev HJ, Zachariae R. Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: a systematic review and meta-analysis. BMJ Open. 2015;5: e006592 10.1136/bmjopen-2014-006592 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref031] 31.Hämmerli K, Znoj H, Barth J. The efficacy of psychological interventions for infertile patients: a meta-analysis examining mental health and pregnancy rate. Hum Reprod Update. 2009;15: 279–295. 10.1093/humupd/dmp002 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref032] 32.Agostini F, Monti F, Andrei F, Paterlini M, Palomba S, La Sala GB. Assisted reproductive technology treatments and quality of life: a longitudinal study among subfertile women and men. J Assist Reprod Genet. 2017;34: 1307–1315. 10.1007/s10815-017-1000-9 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref033] 33.Milazzo A, Mnatzaganian G, Elshaug AG, Hemphill SA, Hiller JE, Astute Health Study Group. Depression and Anxiety Outcomes Associated with Failed Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis. PLoS ONE. 2016;11: e0165805 10.1371/journal.pone.0165805 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref034] 34.Di Paola R, Garzon S, Giuliani S, Laganà AS, Noventa M, Parissone F, et al. Are we choosing the correct FSH starting dose during controlled ovarian stimulation for intrauterine insemination cycles? Potential application of a nomogram based on woman’s age and markers of ovarian reserve. Arch Gynecol Obstet. 2018;298: 1029–1035. 10.1007/s00404-018-4906-2 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref035] 35.Schmidt L, Sobotka T, Bentzen JG, Nyboe Andersen A, ESHRE Reproduction and Society Task Force. Demographic and medical consequences of the postponement of parenthood. Hum Reprod Update. 2012;18: 29–43. 10.1093/humupd/dmr040 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref036] 36.Kitchen H, Aldhouse N, Trigg A, Palencia R, Mitchell S. A review of patient-reported outcome measures to assess female infertility-related quality of life. Health Qual Life Outcomes. 2017;15: 86 10.1186/s12955-017-0666-0 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0238945.ref037] 37.WHOQOL: measuring quality of life. [cited 25 Mar 2020]. Available: https://apps.who.int/iris/handle/10665/63482

[pone.0238945.ref038] 38.Massarotti C, Gentile G, Ferreccio C, Scaruffi P, Remorgida V, Anserini P. Impact of infertility and infertility treatments on quality of life and levels of anxiety and depression in women undergoing in vitro fertilization. Gynecol Endocrinol. 2019;35: 485–489. 10.1080/09513590.2018.1540575 [DOI] [PubMed] [Google Scholar]

[pone.0238945.ref039] 39.Colbert CY, Diaz-Guzman E, Myers JD, Arroliga AC. How to interpret surveys in medical research: a practical approach. Cleve Clin J Med. 2013;80: 423–435. 10.3949/ccjm.80a.12122 [DOI] [PubMed] [Google Scholar]

PERMALINK

Psychosocial and professional burden of Medically Assisted Reproduction (MAR): Results from a French survey

Blandine Courbiere

Arnaud Lacan

Michael Grynberg

Anne Grelat

Virginie Rio

Elisangela Arbo

Céline Solignac

Roles

Abstract

Objective

Materials and methods

Results

Conclusion

Introduction

Materials and methods

Data management and analyses

Results

Demographic and general information

Table 1. MAR burden: A French national survey.

Personal history before resorting to a MAR procedure

Table 2. A French national survey.

Perceptions of and relationship with the infertility healthcare system

Fig 1. Satisfaction concerning health care during the MAR program: A French national survey.

Psychological, physical and social impact (Figs 2–5)

Fig 2. MAR and psychological impact: A French national survey.

Fig 5. MAR burden on social life: A French national survey.

Fig 3. MAR and physical impact: A French national survey.

Fig 4. MAR burden on affective life: A French national survey.

Table 3. A French national survey.

Burden of MAR on professional life (Fig 6)

Fig 6. MAR burden in professional life: A French national survey.

Table 4. MAR and professional burden for women and men who reported to have had a very significant and a rather significant impact on their professional life.

Discussion

Conclusions

Supporting information

Data Availability

Funding Statement

References

Decision Letter 0

Antonio Simone Laganà

Roles

Author response to Decision Letter 0

Decision Letter 1

Antonio Simone Laganà

Roles

Acceptance letter

Antonio Simone Laganà

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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