Fertility return after hormonal contraceptive discontinuation and associated factors among women attended Family Guidance Association of Ethiopia Dessie model clinic, Northeast Ethiopia: A cross-sectional study

Yitayish Damtie; Bereket Kefale; Mastewal Arefaynie; Melaku Yalew; Bezawit Adane

doi:10.1371/journal.pone.0287440

. 2023 Jul 11;18(7):e0287440. doi: 10.1371/journal.pone.0287440

Fertility return after hormonal contraceptive discontinuation and associated factors among women attended Family Guidance Association of Ethiopia Dessie model clinic, Northeast Ethiopia: A cross-sectional study

Yitayish Damtie ^1,^*, Bereket Kefale ², Mastewal Arefaynie ², Melaku Yalew ¹, Bezawit Adane ¹

Editor: Janet E Rosenbaum³

PMCID: PMC10335688 PMID: 37432916

Abstract

Background

Women who use hormonal contraception face delayed return of fertility upon discontinuation. There was limited evidence of fertility return after hormonal contraceptive discontinuation in the study area. Hence this study assessed fertility return after hormonal contraceptive discontinuation and associated factors among pregnant women attending Family Guidance Association Ethiopia (FGAE) Dessie model clinic, Northeast Ethiopia, 2019.

Methods

A cross-sectional study was conducted on 423 samples selected by using systematic random sampling. Data were collected by face-to-face interview using a pretested and structured questionnaire and reviewing client records. Data were entered using Epi Data version 3.1 and analyzed using SPSS version 23. Both bi-variable and multivariable binary logistic regressions were used to identify predictors of delayed fertility return. Adjusted odds ratio (AOR) along with a 95% Confidence Interval (CI) was used to measure the strength and the direction of the association and statistical significance was declared at a P-value less than 0.05.

Result

The proportion of fertility return among currently pregnant women after discontinuation of any hormonal contraceptive methods was 88.6% (95% CI; (85.6%-92%)). The proportion of fertility return among Depo-Provera, implant, Intrauterine Contraceptive Device (IUCD), and Oral Contraceptive Pill (OCP) users was 75%, 99.1%, 100%, and 97.8% respectively. Age, (AOR = 5.37, (95% CI; (1.48, 13.6)) and using Depo-Provera (AOR = 4.82, 95% CI; (1.89, 14.2)) had a significant association with delayed fertility return.

Conclusions

The proportion of fertility return among women after discontinuation of any hormonal contraceptive methods was high. Age and using Depo-Provera had a positive association with delayed fertility return. This study recommends a contraceptive counseling approach that addresses concerns about delay in the return of fertility after hormonal contraceptive discontinuation to avoid confusion among family planning users.

Introduction

A family planning program is an essential and cost-effective health promotion program that has been provided in the African context for more than 50 years [1]. Universal access to family planning can reduce maternal deaths by 40% and infant mortality by 10% [2, 3]. Despite much programmatic success all over the world, only 22% of reproductive-age women used modern contraception, and 17.3% of women had an unmet need for family planning in 2019 [4]. Unmet need for family planning is also high in Sub-saran Africa (SSA) with an estimated 23.5% of women who want to limit or space their births are not using any contraceptive method [5]. In Ethiopia, only 36% of currently married women used contraceptives and 22% of women have an unmet need for family planning [6]. Lack of awareness about contraceptive methods, lack of access to contraceptive information, fear of infertility, and cost of the services are barriers responsible for the huge unmet need for family planning among individuals [5, 7–9].

Delayed return of fertility after discontinuation of contraception becomes a big challenge for women who are using hormonal contraception [10–15]. Although hormonal contraceptive methods are effective, safe, and reversible, they delay fertility upon discontinuation [16–18]. A study showed that 25%, 28%, 25%, and 36% of previous OCP, ICUD, implants, and injectable users experienced a delay in the return of fertility within one year of contraceptive discontinuation [19]. Another study conducted in fifteen SSA countries indicated that 27% of women were unable to become pregnant within a year following the discontinuation of hormonal contraception [20]. Different evidence suggested that Post-pill amenorrhea was observed among previous OCP users [21–25].

Delay in return of fertility after hormonal contraceptive discontinuation had a significant impact on women’s health. It is a repeatedly mentioned reason for not using contraception [26, 27]. It leads to early contraceptive method discontinuation and dissatisfaction with family planning services [28]. The delay in return of fertility following hormonal contraceptive discontinuation is also linked with stigma and discrimination, isolation, intimate partner violence, and mental health disorders [29–31].

Studies showed that different factors have been associated with delayed fertility return. These include age [20, 32], smoking, alcohol drinking [33], parity, gravidity [32, 34], duration of contraceptive use, and type of contraceptive method [15, 35].

There was limited evidence regarding fertility return after hormonal contraceptive discontinuation in the study area. So, this study aimed to assess fertility return after hormonal contraceptive discontinuation and associated factors among pregnant women attending FGAE Dessie Model Clinic. The finding of this study will have paramount importance for policymakers and program designers to design evidence-based interventions to increase the utilization of family planning services.

Material and methods

Study area, study design, and participants

An institution-based cross-sectional study was conducted in FGAE Dessie Model Clinic from May 1–30/2019. FGAE is a volunteer-based, non-government and nonprofit organization that initiate and expand the Sexual and Reproductive Health (SRH) program in Ethiopia since 1966. FGAE Dessie Model clinic which is found in Dessie city administration (located 401KM away from Addis Ababa, the capital city of Ethiopia, and 480km away from Bahir Dar) is one of FGAE SRH clinics established in 1975 and has served more than 100,000 population of all types including key and priority population, most vulnerable and underserved populations of South Wollo administrative zone. It is one of the local Non-governmental Organizations (NGOs) that provide SRH services including youth-friendly services, family planning, antenatal, delivery, postnatal, HIV, and other STI services through its clinic.

The source population was all pregnant women attending the Antenatal Care (ANC) unit of FGAE Dessie Model Clinic whereas; the study population was all systematically selected pregnant women attending the ANC unit of FGAE Dessie Model Clinic during the study period. All systematically selected pregnant women coming for ANC during the data collection period were included and those women who became pregnant without using any contraceptive method and due to contraceptive failure were excluded from the study.

Sample size and sampling procedure

The sample size was determined by using single population proportion formula by considering the proportion of delayed fertility return as 50% since no study was done in Ethiopia, 95% confidence level, and a 5% margin of error. Thus, the final sample size after adding a 10% non-response rate became 423. A systematic random sampling technique was used to select study participants. As the 2018 data showed, on average, a total of 936 pregnant women attended the ANC room of FGAE Dessie model clinic each month. Using this information, interval (k) was determined by dividing the average client flow per month (N) by the total sample size (n) i.e. k = N/n, K = 936/423, K = 2.2≈2. So, study participants were selected every two women until reaching the final sample size.

Data collection procedures and measurements

Data were collected by face-to-face interview using a pretested and structured Amharic version questionnaire taken from previous similar works of literature. The questionnaire was composed of Socio-demographic factors, behavioral factors, obstetric, contraceptive, disease, and nutritional-related factors [15, 20, 32–36]. Two trained nurses have collected the data from May 1–30/2019 under the supportive supervision of one supervisor and principal investigators. Special markings were used to avoid the collection of unnecessary data from cases with repeated visits during the study period.

Data collectors and supervisor were trained for two days on the objective of the study, the content of the questionnaire, and the data collection procedure. Before the data collection, the questionnaire was pretested on 22 study participants at Dessie health center, and based on feedback obtained from the pretest, a necessary modification was done. During the study period, the collected data were checked continuously daily for completeness by the supervisor and principal investigators. Moreover, we have tried to provide adequate time and detailed explanation of questioners for each study participant to minimize memory-related bias (recall bias).

The outcome variable was fertility return after hormonal contraceptive discontinuation. In this study, fertility return was defined if conception occurred within 12 months following discontinuation of any hormonal contraceptive methods (Depo-Provera, OCP, IUCD, and implant) [15, 36].

Abortion: Termination of pregnancy before 28 weeks of gestation. It includes both spontaneous and induced abortion.

The menstrual cycle is the duration between two consecutive menses (the duration from the first day of menses to the first day of the next menses). The cycle is said to be irregular: if a woman’s menstrual cycle is shorter than 21 days or longer than 35 days and, regular: if a cycle ranges from 21 to 35 days.

History of medical illness: Having a previous history of tuberculosis, diabetes, or both.

Khat is a fresh green leafy plant that contains a psycho-active ingredient cathinone. It is classified as an illicit substance due to the potential for psychological dependence. Its regular consumption negatively impacts the human central nervous system, systemic blood pressure, psychological health, and reproductive system causing reproductive toxicity and sexual dysfunction.

Statistical analysis

Data were coded and entered into Epi Data version 3.1 and exported to SPSS version 23 for analysis. Descriptive statistics such as frequency, percentage, and median with Interquartile Range (IQR) were carried out. Bi-variable binary logistic regression was performed and variables with a p-value of less than 0.25 were transported to multivariable logistic regression. Multicollinearity was checked using standard error and Hosmer and Lemeshow goodness of test was used to check model fitness. Variables with a P-value less than 0.05 and AOR with a 95% confidence interval non-inclusive of one were considered as statistically significant predictors of delayed fertility return in the final model.

Ethical approval

Ethical Clearance was taken from the Ethical Review Committee (ERC) of Wollo University College of Medicine and Health Sciences. An official letter was written from the School of Public Health to FGAE Dessie Model Clinic head to get permission. After explaining the purpose of the study, verbal informed consent was taken from each participant before the data collection. They were informed that participating in the study was voluntary and the right to withdraw from the study at any time during the interview was assured. Privacy and confidentiality of information they gave was secured at all levels.

This manuscript was organized and written according to strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 2007 (v4) Statement checklist for cross-sectional studies (S1 Table).

Results

Socio-demographic characteristics

In this study, a total of 402 pregnant women were involved and making a response rate of 94.5%. The median age of the respondents was 28 years with an IQR of 4 years. Three hundred eighty (94.5%) of pregnant women were married and 361(89.8%) of pregnant women were Amhara in their ethnicity respectively. Two hundred sixteen (53.7%) pregnant women were orthodox tewahido followers, 203(50.5%) of women earn less than or equal to 94.3 American Dollars, and 392 (97.5%) of women live in urban areas respectively. One hundred ninety-six (48.8%) of pregnant women were educated up to college and university level and 143(35.6%) of women were government employed respectively (Table 1).

Table 1. Socio-demographic characteristics of pregnant women who attended FGAE Dessie model clinic, Northeast Ethiopia, 2019.

Variable	Frequency (n = 402)	Percentage (%)
Age
15–24	78	19.4
25–34	295	73.4
≥35	29	7.2
Marital status
Single	10	2.5
Married	380	94.5
Divorced	12	3.0
Ethnicity
Amhara	361	89.8
Oromo	23	5.7
Tigray	18	4.5
Income
≤94.3$	203	50.5
94.4–188.7$	163	40.5
>188.8$	36	9.0
Religion
Orthodox tewahido	216	53.7
Muslim	175	43.5
Protestant	11	2.7
Residence
Urban	392	97.5
Rural	10	2.5
Educational status
No formal education	17	4.2
Grade 1–8	65	16.2
Grade 9–12	124	30.8
College and above	196	48.8
Occupation
Government employ	143	35.6
Private employ	48	11.9
Housewife	149	37.1
Merchant	54	13.4
Farmer	3	.7
Daily laborer	5	1.2

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Behavioral characteristics

One hundred thirty-one (32.6%) of pregnant women ever drink alcohol in their lifetime, 121(30.1%) of women drink alcohol in the last twelve months and 64 (15.9%) of women drink alcohol less than once a month in the last twelve months respectively. Seventy-one (17.7%) of pregnant women ever chew khat in their lifetime, 51(12.7%) of women chewed khat in the last twelve months and 17 (4.2%) of women chew khat less than once a month in the last twelve months respectively. In the case of frequency of sexual intercourse, 71 (17.7%) and 219 (54.5%) of pregnant women had sexual intercourse three times a day and three times a week respectively (Table 2).

Table 2. Behavioral characteristics of pregnant women who attended FGAE Dessie model clinic, Northeast Ethiopia, 2019.

Variables	Frequency (n = 402)	Percentage (%)
Ever drink alcohol
Yes	131	32.6
No	271	67.4
Alcohol use within 12 months
Yes	121	30.1
No	10	2.5
Frequency of alcohol use
Daily	1	0.2
One to four days per week	3	0.7
One to three days per month	53	13.2
Less than once a month	64	15.9
Ever chew khat
Yes	71	17.7
No	331	82.3
Chew khat within 12 months
Yes	51	12.7
No	20	5.0
Frequency of chewing
Monthly	5	1.2
Less than once a month	17	4.2
Rarely	29	7.2
Frequency of sexual intercourse
Three times a day	71	17.7
Three times a week	219	54.5
Three times a month	102	25.4
Three times a year	10	2.5

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Contraceptive, obstetric, and disease-related characteristics

The majority 172(42.8%) of pregnant women used Depo-Provera and 113 (28.1%) women used implants as a contraceptive method before the current pregnancy. One hundred eighty-four (45.8%) of pregnant women used contraceptive methods for 12–24 months before the current pregnancy. One hundred fifty-eight (39.3%) of women have given birth once, 30 (7.5%) of pregnant women had a history of abortion, and 301(74.9%) of pregnant women had regular menstrual cycles before the current pregnancy. Four (1%) and 6(1.5%) of pregnant women had a history of Sexual Transmitted Infection (STI) and other medical illnesses (tuberculosis and diabetic Malthus) respectively (Table 3).

Table 3. Contraceptive, obstetric, and disease-related characteristics of pregnant women attended FGA Dessie model clinic, Northeast Ethiopia, 2019.

Variables	Frequency (n = 402)	Percentage (%)
Type of contraceptive used
OCP	91	22.6
Depo-Provera	172	42.8
Implant	113	28.1
IUCD	26	6.5
Duration of contraceptive use
<12 month	107	26.6
12–24 month	184	45.8
25–36 month	63	15.7
>36 month	48	11.9
Number of births
Never give birth	92	22.9
1	158	39.3
≥2	152	37.8
History of abortion
Yes	30	7.5
No	372	92.5
Menstrual cycle
Irregular	101	25.1
Regular	301	74.9
History of STI
Yes	4	1.0
No	398	99.0
History of medical illness
Yes	6	1.5
No	396	98.5

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The proportion of fertility return

The proportion of fertility return among pregnant women after discontinuation of any hormonal contraceptive methods before the current pregnancy was 88.6% (95% CI; (85.6–92%)).

The proportion of fertility return among pregnant women who used Depo-Provera, implant, IUCD, and OCP before the current pregnancy was 75% (95% CI; (68.6%-80.8%)), 99.1% (95% CI; (97.3–99.999%)), 100% and 97.8% respectively.

The median time of fertility return among pregnant women after discontinuation of any hormonal contraceptive methods before the current pregnancy was 6 months with an IQR of 8 months. The median time of fertility return among Depo-Provera implant, IUCD, and OCP users before the current pregnancy was 9 months, 4 months, 6 months, and 2 months with IQR of 7 months, 4 months, 8 months, and 4 months respectively.

Factors associated with delayed fertility return

Both bi-variable and multivariable binary logistic regression analyses were done. The finding indicated that pregnant women aged 35 years and more were 5.4 times more likely to experience fertility delay upon hormonal contraceptive discontinuation compared to their counterparts (AOR = 5.37, (95% CI; (1.48, 13.6)). Similarly, pregnant women who used Depo-Provera before the current pregnancy were 4.8 times more likely to experience fertility delay upon discontinuation as compared to women who used implant, IUCD, and OCP (AOR = 4.82, 95% CI; (1.89, 14.2)) (Table 4).

Table 4. Factors associated with delayed fertility return after hormonal contraceptive discontinuation among pregnant women attended FGAE Dessie model clinic, Northeast Ethiopia, 2019.

Variables	Fertility return (n = 402)		COR (95% CI)	AOR (95% CI)
Variables	Delayed	Not delayed	COR (95% CI)	AOR (95% CI)
Age
15–24	6 (13%)	72 (20.2%)	1	1
25–34	33 (71.7%)	262 (73.6%)	1.51 (0.61, 3.75)	1.35 (0.44, 4.15)
≥35	7 (15.2%)	22(6.2%)	3.82 (1.16, 12.6)	5.37 (1.48, 13.6)^*
Monthly Income
≤94.3$	26 (56.5%)	177 (49.7%)	1	1
94.4–188.7$	17 (37.0%)	146 (41.0%)	0.79 (0.41, 1.52)	0.90 (0.39, 2.04)
>188.8$	3 (6.5%)	33 (9.3%)	0.62 (0.18, 2.16)	1.18 (0.24, 5.75)
Educational status
No formal education	6 (13.0%)	11 (3.1%)	4.55(1.52, 13.6)^*	2.63 (0.41, 16.94)
Grade 1–8	8 (17.4%)	57 (16.0%)	1.17 (0.49, 2.8)	1.27 (0.31, 5.21)
Grade 9–12	11 (23.9%)	113 (31.7%)	0.81 (0.38, 1.7)	0.48 (0.14, 1.57)
College and above	21 (45.7%)	175 (49.2%)	1	1
Ever drink alcohol
Yes	15 (32.6%)	116 (32.6%)	1.01 (0.52, 1.9)	1.14 (0.48, 2.72)
No	31 (67.4%)	240 (67.4%)	1	1
Ever chew Khat
Yes	11 (23.9%)	60 (16.9%)	1.55 (0.75, 3.2)	0.99 (0.27, 3.62)
No	35 (76.1%)	296 (83.1%)	1	1
Duration of contraceptive use
<12 month	10 (21.7%)	97 (27.2%)	1	1
12–24 month	23 (50.0%)	161 (45.2%)	1.39 (0.63, 3.04)	1.02 (0.39, 2.62)
25–36 month	6 (13.0%)	57 (16.0%)	1.02 (0.35, 2.96)	1.28 (0.36, 4.49)
>36 month	7 (15.2%)	41 (11.5%)	1.66 (0.59, 4.65)	1.10 (0.28, 4.36)
Number of births
Never give birth	9 (19.6%)	83 (23.3%)	0.81 (0.35, 1.88)	1.67 (0.49, 5.61)
1	19 (41.3%)	139 (39%)	1.02 (0.51, 2.02)	1.19 (0.47, 3.01)
≥2	18 (39.1%)	134 (37.6%)	1	1
Menstrual cycle
Irregular	19 (41.3%)	82 (23.0%)	2.4 (1.24,4.44)^**	1.21 (0.53, 2.75)
Regular	27 (58.7%)	274 (77.0%)	1	1
MUAC	46 (11.4%)	356(88.6%)	0.92 (0.79, 1.07)	0.99 (0.82, 1.20)
Occupation
Government employ	17 (37.0%)	126 (35.4%)	1	1
Private employ	4 (8.7%)	44 (12.4%)	0.67 (0.22, 2.11)	0.73 (0.19, 2.87)
Housewife	14 (30.4%)	135 (37.9%)	0.77 (0.36, 1.62)	0.47 (0.13, 1.74)
Others^c	11 (23.9%)	51 (14.3%)	1.60 (0.70, 3.65)	0.98 (0.27, 3.67)
Frequency of sexual intercourse
Three times a day	10 (21.7%)	61 (17.1%)	1	1
Three times a week	24 (52.2%)	195 (54.8%)	0.751(0.34,1.68)	0.65 (0.18, 2.33)
Others^d	12 (26.1%)	100 (28.1%)	0.732(0.34,1.80)	0.48 (0.11, 2.09)
Type of contraceptive
Depo-provera	43 (93.5%)	129 (36.2%)	3.21 (1.67, 13.3)^***	4.82 (1.89, 14.2)^***
Others ^e	3(6.5%)	227(63.8%)	1	1

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COR, crude odds ratio; AOR, adjusted odds ratio; MUAC, middle-upper arm circumference

*significant at P<0.05

** significant at P<0.01

*** significant at P ≤ 0.001 in the bi-variable and multivariable logistic regression analysis

^c merchant, farmer, and daily laborer

^d three times a month and three times a year

^e IUCD and OCP.

Discussion

The proportion of fertility return after discontinuation of any hormonal contraceptive methods before the current pregnancy was 88.6%. The proportion of fertility return among Depo-Provera, implant, IUCD, and OCP users before the current pregnancy was 75%, 99.1%, 100%, and 97.8% respectively. Age and using Depo-Provera had a positive association with delayed fertility return.

The proportion of fertility return among pregnant women after discontinuation of any hormonal contraceptive methods was 88.6%. the finding is similar to a study conducted by Farrow A et al in England which showed that 82% of the participants conceived within one year after discontinuation of any hormonal contraceptive method [36]. However, it is higher than studies conducted by Barden-O’Fallon et al in fifteen SSA countries and Girum T et al which is 73% and 83.1% respectively [15, 20].

The proportion of fertility return among Depo-Provera users before the current pregnancy was similar but, the proportion of fertility return among implant, IUCD, and OCP users was high as compared to a meta-analysis study conducted by Girum T et al which indicated that the proportion of fertility return among Depo-Provera, implant, IUCD, and OCP users was 77.7%, 74.7%, 84.7%, and 88% [15]. Similarly, the proportion of fertility return among Depo-Provera, implant, IUCD, and OCP users was high as compared to a study conducted by Gayatri M et al in Indonesia [37]. The proportion of fertility return among IUCD users was also high as compared to a study conducted by Stoddard AM et al in the United States of America and Tadesse E which was 81% and 86.1% respectively [34, 38]. The discrepancy could be due to differences in the study setting, study period, and study population.

In this study, age has a significant association with delayed fertility return. The finding is similar to studies conducted by Farrow A et al, Buckshee K et al, Sivin I et al and Barden-O’Fallon et al [20, 36, 39, 40]. The reason behind this could be the number of eggs decreases as women get older due to a fixed number of eggs in the ovary. The other reason could be as age increases, women will be at higher risk of disorders that can affect fertility, such as uterine fibroids and endometriosis. Moreover, as age increases, the remaining eggs in older women are more likely to have abnormal chromosomes [41, 42].

Using Depo-Provera had a positive association with delayed fertility return. A global handbook on family planning for healthcare providers demonstrated that Depo-Provera causes a delayed fertility return [31]. The finding is also consistent with studies conducted by Yland JJ et al and Pardthaisong T et al [43, 44], This could be due to Depo-Provera can stay in the body system longer than the other birth control methods so that the clearance of progestin from the serum takes a long time and the meantime to ovulation become delayed. On the other hand, Depo-Provera causes excessive weight gain; these leads women to stop ovulation and get irregular menstrual cycles. Once women stop ovulation, they would not be able to conceive and therefore it delays fertility return.

This study has limitations. Some variables like a history of alcohol use, chat chewing, duration of contraceptive use, sexual behavior, and duration of hormonal contraceptive discontinuation until the current pregnancy will be affected by recall bias. Being a facility-based study will also underestimate fertility return as it is prone to miss defaulters and delayed visitors to their ANC appointment.

Conclusion

The proportion of fertility return among pregnant women after discontinuation of any hormonal contraceptive methods before the current pregnancy was high. Age and using Depo-Provera had a positive association with delayed fertility return. The Ministry of Health should design a contraceptive counseling approach that addresses concerns about delays in the return of fertility after contraceptive discontinuation to avoid confusion among family planning users.

Supporting information

S1 Table. STROBE checklist.

(DOCX)

Click here for additional data file.^{(20.8KB, docx)}

S1 Dataset. The data set used to assess fertility return after hormonal contraceptive discontinuation and associated factors among pregnant women attending Family Guidance Association Ethiopia (FGAE) Dessie model clinic.

(SAV)

Click here for additional data file.^{(27.2KB, sav)}

Acknowledgments

We would like to extend our appreciation to FGA Dessie Model Clinic Head and staff, study participants, data collectors, and supervisor for their cooperation during the data collection process.

List of abbreviations

ANC: Antenatal Care
AOR: Adjusted odds ratio
CI: Confidence Interval
FGAE: Family Guidance Association of Ethiopia
IQR: Inter Quartile Range
IUCD: Uterine Contraceptive Device
OCP: Oral Contraceptive Pill
STI: Sexual Transmitted Infection
SSA: Sub-Saharan Africa

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

1.Olson DJ, Piller A. Ethiopia: an emerging family planning success story. Studies in family planning 2013; 44(4):445–459. doi: 10.1111/j.1728-4465.2013.00369.x [DOI] [PubMed] [Google Scholar]
2.USAID. Update on family planning in Sub-Saharan Africa. Repositioning family planning: guidelines for advocacy action. Washington: Academy for Educational Development; 2009. [Google Scholar]
3.Smith R, Ashford L, Gribble J, Clifton D: Family planning saves lives. Washington DC: Population Reference Bureau; 2009, 5. [Google Scholar]
4.United Nations DoE, Social Affairs PD: Contraceptive Use by Method 2019: Data Booklet (ST/ESA/SER. A/435). In.: United Nations, Department of Economic and Social Affairs, Population Division; 2019. [Google Scholar]
5.Sedgh G, Hussain R: Reasons for contraceptive nonuse among women having an unmet need for contraception in developing countries. Studies in family planning 2014, 45(2):151–169. [DOI] [PubMed] [Google Scholar]
6.Central Statistical Agency Addis Ababa Ethiopia. Demographic and Health Survey 2016. Federal Democratic Republic of Ethiopia; 2017. [Google Scholar]
7.Campbell M, Sahin‐Hodoglugil NN, Potts M: Barriers to fertility regulation: a review of the literature. Studies in family planning 2006, 37(2):87–98. doi: 10.1111/j.1728-4465.2006.00088.x [DOI] [PubMed] [Google Scholar]
8.Gueye A, Speizer IS, Corroon M, Okigbo CC: Belief in family planning myths at the individual and community levels and modern contraceptive use in urban Africa. International Perspectives on Sexual and reproductive health 2015, 41(4):191. doi: 10.1363/4119115 [DOI] [PMC free article] [PubMed] [Google Scholar]
9.Diamond-Smith N, Campbell M, Madan S: Misinformation and fear of side-effects of family planning. Culture, health & Sexuality 2012, 14(4):421–433. doi: 10.1080/13691058.2012.664659 [DOI] [PubMed] [Google Scholar]
10.Okenwa L, Lawoko S, Jansson B: Contraception, reproductive health, and pregnancy outcomes among women exposed to intimate partner violence in Nigeria. The European Journal of Contraception & Reproductive Health Care 2011, 16(1):18–25. doi: 10.3109/13625187.2010.534515 [DOI] [PubMed] [Google Scholar]
11.Zhu H, Lei H, Huang W, Fu J, Wang Q, Shen L, et al. : Fertility in older women following removal of long-term intrauterine devices in the wake of a natural disaster. Contraception 2013, 87(4):416–420. doi: 10.1016/j.contraception.2012.11.002 [DOI] [PubMed] [Google Scholar]
12.Delbarge W, Batar I, Bafort M, Bonnivert J, Colmant C, Dhont M, et al. : Return to fertility in nulliparous and parous women after removal of the GyneFix® intrauterine contraceptive system. The European Journal of Contraception & Reproductive Health Care 2002, 7(1):24–30. [PubMed] [Google Scholar]
13.Issa AA, Amr MF: Fertility after removal of intrauterine contraceptive devices. Current therapeutic research 1998, 59(4):257–261. [Google Scholar]
14.Mansour D, Gemzell-Danielsson K, Inki P, Jensen JT: Fertility after discontinuation of contraception: a comprehensive review of the literature. Contraception 2011, 84(5):465–477. doi: 10.1016/j.contraception.2011.04.002 [DOI] [PubMed] [Google Scholar]
15.Girum T, Wasie A: Return of fertility after discontinuation of contraception: a systematic review and meta-analysis. Contraception and reproductive medicine 2018, 3(1):1–9. doi: 10.1186/s40834-018-0064-y [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Jacobstein R: Long-acting and permanent contraception: an international development, service delivery perspective. Journal of Midwifery & women’s Health 2007, 52(4):361–367. doi: 10.1016/j.jmwh.2007.01.001 [DOI] [PubMed] [Google Scholar]
17.Kulier R, O’Brien P, Helmerhorst FM, Usher‐Patel M, d’Arcangues C: Copper containing, framed intra‐uterine devices for contraception. Cochrane Database of systematic reviews 2007(4). doi: 10.1002/14651858.CD005347.pub3 [DOI] [PubMed] [Google Scholar]
18.Brief BP: Prevention of Postpartum Hemorrhage in Rural Ethiopia. 2012. [Google Scholar]
19.Gayatri M, Utomo B, Budiharsana M: How soon can you expect to get pregnant after discontinuing the reversible contraceptive method? A survival analysis of the 2017 Indonesia demographic and health survey data. EXECUTIVE EDITOR 2020, 11(01):310. [Google Scholar]
20.Barden-O’Fallon J, Speizer IS, Calhoun LM, Moumouni NA: Return to pregnancy after contraceptive discontinuation to become pregnant: a pooled analysis of West and East African populations. Reproductive Health 2021, 18(1):1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Shearman R: Amenorrhea after treatment with oral contraceptives. Lancet (London, England) 1966, 2(7473):1110. doi: 10.1016/s0140-6736(66)92197-0 [DOI] [PubMed] [Google Scholar]
22.Vessey M, Wright N, McPherson K, Wiggins P: Fertility after stopping different methods of contraception. Br Med J 1978, 1(6108):265–267. doi: 10.1136/bmj.1.6108.265 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Linn S, Schoenbaum SC, Monson RR, Rosner B, Ryan KJ: Delay in conception for former’pill’users. Jama 1982, 247(5):629–632. [PubMed] [Google Scholar]
24.Harlap S, Baras M: Conception-waits in fertile women after stopping oral contraceptives. International Journal of Fertility 1984, 29(2):73–80. [PubMed] [Google Scholar]
25.Chasan-Taber L, Willett WC, Stampfer MJ, Spiegelman D, Rosner BA, Hunter DJ, et al. : Oral contraceptives and ovulatory causes of delayed fertility. American journal of Epidemiology 1997, 146(3):258–265. doi: 10.1093/oxfordjournals.aje.a009261 [DOI] [PubMed] [Google Scholar]
26.Castle S: Factors influencing young Malians’ reluctance to use hormonal contraceptives. In.: Wiley Online Library; 2003. [DOI] [PubMed] [Google Scholar]
27.Ochako R, Mbondo M, Aloo S, Kaimenyi S, Thompson R, Temmerman M, et al. : Barriers to modern contraceptive methods uptake among young women in Kenya: a qualitative study. BMC public health 2015, 15(1):1–9. doi: 10.1186/s12889-015-1483-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
28.Burke H, Ambasa-Shisanya C: Qualitative study of reasons for discontinuation of injectable contraceptives among users and salient reference groups in Kenya. African Journal of reproductive health 2011, 15(2). [PubMed] [Google Scholar]
29.Fotherby K, Yong-En S, Howard G, Elder M, Muggeridge J: Return of ovulation and fertility in women using norethisterone oenanthate. Contraception 1984, 29(5):447–455. doi: 10.1016/0010-7824(84)90018-0 [DOI] [PubMed] [Google Scholar]
30.Pardthaisong T, Gray R, Mcdaniel E: Return of fertility after discontinuation of depot medroxyprogesterone acetate and intra-uterine devices in Northern Thailand. The Lancet 1980, 315(8167):509–512. doi: 10.1016/s0140-6736(80)92765-8 [DOI] [PubMed] [Google Scholar]
31.Organization WH: Family planning: a global handbook for providers: 2011 update: evidence-based guidance developed through worldwide collaboration. 2011. [Google Scholar]
32.Vessey MP, Smith M, Yeates D: Return of fertility after discontinuation of oral contraceptives: influence of age and parity. Br J Fam Plann 1986, 11(4):120–124. [Google Scholar]
33.Buck GM, Sever LE, Batt RE, Mendola P: Life-style factors and female infertility. Epidemiology 1997:435–441. doi: 10.1097/00001648-199707000-00015 [DOI] [PubMed] [Google Scholar]
34.Stoddard AM, Xu H, Madden T, Allsworth JE, Peipert JF: Fertility after intrauterine device removal: a pilot study. The European Journal of Contraception & Reproductive Health Care 2015, 20(3):223–230. doi: 10.3109/13625187.2015.1010639 [DOI] [PMC free article] [PubMed] [Google Scholar]
35.Wallach EE, Huggins GR, Cullins VE: Fertility after contraception or abortion. Fertility and sterility 1990, 54(4):559–573. doi: 10.1016/s0015-0282(16)53808-4 [DOI] [PubMed] [Google Scholar]
36.Farrow A, Hull M, Northstone K, Taylor H, Ford W, Golding J: Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception. Human Reproduction 2002, 17(10):2754–2761. doi: 10.1093/humrep/17.10.2754 [DOI] [PubMed] [Google Scholar]
37.Gayatri M, Utomo B, Budiharsana M, Dasvarma G: Pregnancy resumption following contraceptive discontinuation: Hazard survival analysis of the Indonesia Demographic and Health Survey Data 2007, 2012 and 2017. Plos one 2022, 17(2):e0264318. doi: 10.1371/journal.pone.0264318 [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Tadesse E: Return of fertility after an IUD removal for planned pregnancy: a six-year prospective study. East African medical journal 1996, 73(3):169–171. [PubMed] [Google Scholar]
39.Buckshee K, Chatterjee P, Dhall G, Hazra M, Kodkany B, Lalitha K, et al. : Return of fertility following discontinuation of norplantR-II subdermal implants: ICMR task force on hormonal contraception. Contraception 1995, 51(4):237–242. [DOI] [PubMed] [Google Scholar]
40.Sivin I, Stern J, Diaz S, Pavéz M, Alvarez F, Brache V, et al. : Rates and outcomes of planned pregnancy after use of Norplant capsules, Norplant II rods, or levonorgestrel-releasing or copper TCu 380Ag intrauterine contraceptive devices. American Journal of obstetrics and Gynecology 1992, 166(4):1208–1213. doi: 10.1016/s0002-9378(11)90607-3 [DOI] [PubMed] [Google Scholar]
41.Hook EB: Rates of chromosome abnormalities at different maternal ages. Obstetrics and gynecology 1981, 58(3):282–285. [PubMed] [Google Scholar]
42.Capezzuoli T, Vannuccini S, Fantappiè G, Orlandi G, Rizzello F, Coccia ME, et al. : Ultrasound findings in infertile women with endometriosis: evidence of concomitant uterine disorders. Gynecological Endocrinology 2020, 36(9):808–812. doi: 10.1080/09513590.2020.1736027 [DOI] [PubMed] [Google Scholar]
43.Yland JJ, Bresnick KA, Hatch EE, Wesselink AK, Mikkelsen EM, Rothman KJ, et al. : Pregravid contraceptive use and fecundability: prospective cohort study. bmj 2020, 371. doi: 10.1136/bmj.m3966 [DOI] [PMC free article] [PubMed] [Google Scholar]
44.Pardthaisong T: Return of fertility after use of the injectable contraceptive Depo Provera: updated data analysis. Journal of Biosocial Science 1984, 16(1):23–34. doi: 10.1017/s0021932000014760 [DOI] [PubMed] [Google Scholar]

PLoS One. doi: 10.1371/journal.pone.0287440.r001

Decision Letter 0

Janet E Rosenbaum

22 Feb 2022

PONE-D-21-25440Fertility return after contraceptive discontinuation and associated factors among women attended Family Guidance Association of Dessie model clinic, Northeast Ethiopia: a cross-sectional studyPLOS ONE

Dear Dr. Damtie,

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**********

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Reviewer #1: Comments

1. Introduction ..the first paragraph is unnecessary( It talks about infertility and....).

2.The fourth paragraph is unnecessary...The introduction should focus on fertility return after contraceptive discontinuation and associated factors ..but I didn't see about associated factors

3. Methods: How do you control reputation of cases. The same patient might came twice per week or weekly.

4. I wonder that you get more than 400 pregnant mothers who fulfills the study criteria within a month (even less than 22 days in one clinic). I have a question on the reliability of the data.

5.There were ampoule studies related to your title in Ethiopia.. please search more. E.g.[https://pubmed.ncbi.nlm.nih.gov/8698014/)

6. This study had a lot of confounders especially memory related, sexually behavior to get pregnant.[ They may discontinued due to side effects or other different reasons.] What was done to minimize thus confounders?

7. What does mean 'unit increase in age...'

8. What is your base to define delayed fertility after 12 months. Or operational definition?

9. Discussion is superficial

10. conclusion: Is so elementary...should be improved.

Reviewer #2: Title: the title “Fertility return after contraceptive discontinuation and associated factors

among women” is about fertility return after discontinuation, however, what I presented in the result is proportion if delayed fertility, which is the other way around. So it is better described as per the research topic and the objectives

Abstract

� Result: the phrase “Uterine contraceptive device has to be replaced by Intrauterine contraceptive device”

� The percentages have to be out of the parenthesis.

� The conclusion is not clear. Was there a negative effect of contraception on fertility or not? This must be answered.

� Recommendation stating “the need for counseling of clients by health provider” is not from of this research findings. Better to have conclusion based on the research findings.

Introduction

• The terms, Delayed fertility and infertility are confused. Better to have standard or operational definition of this terms as they are quite different.

Methods

• The authors described that they have selected the study subjects by SRS, what was the sampling frame? This is health facility study and the subjects usually be enrolled consecutively until the sample size is achieved

• My question on the definition of delayed fertility is answered here, however, it is not similar with infertility and the term infertility or delayed fertility must not be used interchangeably.

• How did you confirm that all are pregnant? At what gestational age did you include them? if majority are in the second trimester you might have excluded women who were pregnant and had abortions in the first trimester, which occurs at least in 15% of the cases. Or you have to put this as a limitation of this study.

Result

• Where is the age of the participants? Age is a very crucial variable to talk about fertility. Better to show the age distribution of the women especially for those with delayed fertility, because age is a factor for fertility return.

• The frequency of sexual intercourse, in the part of others must be reclassified as these are many. Because the women with delayed fertility most likely be in this group.

• Gestational age must have been included in the obstetrics variables of the study participants to know the proportion of trimesters. If majority are in the second trimester and above, there a possibility to miss those ladies who had abortion and couldn’t be found at ANC which affects the overall proportion of women had return in fertility.

• Thus, all the possible confounders of return in fertility other than contraception must have been dealt with.

Discussion

• It is very brief and more literatures need to be used.

• Age was found to be a significant factor to affect fertility. Age above which limit? <18? >35? A unity increase in age above what? This has to be clear. Because it is known that early age and late age is associated with anovulation and late age and there may be a deal in fertility normally irrespective of contraception use.

• All the limitations should be stated.

Conclusion and recommendation

• The conclusion and recommendation have to be clear. What is the general conclusion? is the fertility return High or low? What will be the recommendation? Did the contraception use affect the return in fertility differently in your study area than others? What message do you convey to the public?

Reviewer #3: I have uploaded more extensive comments.

However, this article needs to be edited substantially for clarity. There are a lot of phrases that aren’t entirely clear and many details that are not included or are not elaborated upon sufficiently. The methods seem reasonable overall, but lack detail relevant to fully understand. The researchers seem to make a variety of assumptions regarding the data that are not fully explained.

**********

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Reviewer #1: Yes: Endalkachew Mekonnen Assefa

Reviewer #2: No

Reviewer #3: No

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PLoS One. 2023 Jul 11;18(7):e0287440. doi: 10.1371/journal.pone.0287440.r002

Author response to Decision Letter 0

12 Apr 2022

Janet E Rosenbaum, Ph.D

Academic Editor, PLOS ONE

RE: Submission ID PONE-D-21-25440 R1 (Fertility return after contraceptive discontinuation and associated factors among women attended Family Guidance Association of Dessie model clinic, Northeast Ethiopia: a cross-sectional study)

Dear Dr. Janet E Rosenbaum,

Thank you very much for your email and the comments/suggestions of the reviewers and academic editor. We have looked at the comments and have revised our paper accordingly. We hope our paper improved as a result of incorporating the reviewers' and academic editor's comments and suggestions.

Please find for your kind consideration the following:

� A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

� A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

� An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

While hoping that these changes would meet with your favourable consideration, we are happy to hear if there are more comments and suggestions. Please do not hesitate to let us know if you have any questions.

Yours Sincerely,

Yitayish Damtie

School of Public Health, Wollo University

Dessie, Ethiopia

Tel:+251943517982

E-mail: yitutile@gmail.com

Point by point response

Reviewer Comments

Reviewer 1

Introduction:

Comment 1: The first paragraph is unnecessary (It talks about infertility and....)

Response: Thank you dear reviewer. We have amended it.

Comment 2: The fourth paragraph is unnecessary...The introduction should focus on fertility return after contraceptive discontinuation and associated factors...But I didn't see about associated factors.

Response: Thank you. The comment is accepted and addressed accordingly. You can find the associated factors in the introduction section line 71-74

Method:

Comment 3: How do you control reputation of cases? The same patient might came twice per week or weekly.

Response: Thank you for your constructive comment. It is true that the same patient might came twice per week or weekly. We put special markings on all study participants card immediately after data collection to avoid unnecessary collection of data from cases with repeated visit during the study period. We have tried to put this in the method section line 113-114.

Comment 4: I wonder that you get more than 400 pregnant mothers who fulfills the study criteria within a month (even less than 22 days in one clinic). I have a question on the reliability of the data.

Response: Thank you for your constructive comment. During research proposal development, we have tried to collect preliminary information regarding the number of pregnant women attended ANC unit of FGA of Dessie model clinic in 2018(a year before the study was conducted). As the 2018 report showed, more than 900 pregnant women on average attended ANC unit each month. So this is more than enough to get 402 pregnant women who fulfill the inclusion criteria within a month. In the real scenario most pregnant women including me prefer to receive ANC service from FGA dessie model clinic. Due to this the client flow is high in this clinic.

Comment 5: Line 90: “…….. From previous similar works of literature” Was it validated? Since, u said this is the first study in Ethiopia.

Response: Thank you for your constructive comment. We have checked the content and face validity of the tool by experts that have knowledge and research experience related to the subject matter.

Comment 6: There were ampoule studies related to your title in Ethiopia... please search more. E.g. [https://pubmed.ncbi.nlm.nih.gov/8698014/)

Response: Thank you. We have tried to modify the document by searching more literatures related to our title.

Comment 7: This study had a lot of confounders especially memory related, sexually behavior to get pregnant. [They may discontinued due to side effects or other different reasons.] What was done to minimize thus confounders?

Response: Thank you dear reviewer for your constructive comment. To minimize memory related bias (recall bias), we have tried to design questioner carefully, explain questions in detail and provide adequate time for each study participants for better memorization. However, since recall bias cannot be eliminated in observational studies, we have tried to acknowledge it in the limitations of our study. In addition we have tried to conduct multivariable logistic regression analysis to control the effect of confounding variables.

Comment 8: What does mean 'unit increase in age...?’

Response: Thank you. We have try to modify it accordingly.

Comment 9: What is your base to define delayed fertility after 12 months? Or operational definition?

Response: Thank you dear reviewer. It is just operational definition.

Discussion:

Comment 10. Discussion is superficial

Response: Thank you. We have tried to modify the discussion section by searching more literatures related to our title

Comment 11: Line 208-209: (Moreover, as age increases, the remaining eggs in older women are more likely to have abnormal chromosomes. What does it mean?

Thank you for your comment. To make it clear, as the age of the women increase, the number and quality of eggs decreases naturally and progressively from time to time until she reaches menopause causing subfertility. In addition, older age women more likely to have chromosomal problems in their mature eggs. This is because errors in meiosis are more likely to occur as a result of the aging process. Meiosis is the process in which sex cells divide and create new sex cells with half the number of chromosomes. Normally, meiosis causes each parent to give 23 chromosomes to a pregnancy. When a sperm fertilizes an egg, the union leads to a baby with 46 chromosomes. But if meiosis doesn’t happen normally, a baby may have abnormal chromosome or in other words, a baby may have an extra chromosome (trisomy), or have a missing chromosome (monosomy). These problems can cause early pregnancy loss even before the mother notice it.

Conclusion:

Comment 12: Is so elementary...should be improved.

Response: Thank you dear reviewer. We have tried revise the conclusion section accordingly.

Reviewer 2

Title:

Comment 1: The title “Fertility return after contraceptive discontinuation and associated factors

Response: Thank you dear reviewer. We have try to modify the result section accordingly.

Abstract

Comment 2: Line 28: which data was obtained from review of clients' records? Is interview not enough?

Response: Thank you dear reviewer for your important comment. Almost all the women’s data were obtained through face-to-face interview. However for those women who forgotten their last normal menstrual period, information on last normal menstrual period was obtained by reviewing client records.

Comment 3: Result: the phrase “Uterine contraceptive device has to be replaced by intrauterine contraceptive device”

Response: Thank you for your important comment. The comment is accepted and addressed accordingly in the abstract section line 35.

Comment 4: The percentages have to be out of the parenthesis.

Response: Thank you. We have amended it.

Comment 5: The conclusion is not clear. Was there a negative effect of contraception on fertility or not? This must be answered.

Response: Thank you. We have tried to modify the conclusion accordingly.

Comment 6: Recommendation stating “the need for counseling of clients by health provider” is not from of this research findings. Better to have conclusion based on the research findings.

Response: Thank you dear reviewer for your important comment. We have amended the recommendation accordingly.

Introduction:

Comment 7: The terms, Delayed fertility and infertility are confused. Better to have standard or operational definition of this terms as they are quite different. Infertility is defined when a couple is unable to conceive in 12 months with unprotected adequate sexual intercourse. And usually it may have an obvious cause and it needs treatment to achieve conception. However, delayed fertility is subfertility,

Response: Thank you dear reviewer. We have amended the introduction part accordingly.

Method:

Comment 8: The authors described that they have selected the study subjects by SRS, what was the sampling frame? This is health facility study and the subjects usually be enrolled consecutively until the sample size is achieved.

Response: Thank you for your constructive comment. To make it brief, systematic random sampling technique was used to select study participants rather than purposive sampling. As the 2018 data showed, on average, a total of 936 pregnant women attended ANC room of FGA Dessie model clinic in every month. Using this information, interval (k) was determined by dividing the average client flow per month (N) to the total sample size (n) i.e. k=N/n, K=936/423, K=2.2≈2. So, study participants were selected in every two women until reaching the final sample size. We have amended the study population as “all systematically selected pregnant women attending ANC room of FGA Dessie Model Clinic during the study period”.

Comment 9: My question on the definition of delayed fertility is answered here, however, it is not similar with infertility and the term infertility or delayed fertility must not be used interchangeably.

Response: Thank you. The comment is accepted and addressed accordingly.

Comment 10: How did you confirm that all are pregnant? At what gestational age did you include them? If majority are in the second trimester you might have excluded women who were pregnant and had abortions in the first trimester, which occurs at least in 15% of the cases. Or you have to put this as a limitation of this study.

Response: Thank you for your important comment. This study was conducted among women who have already been registered as pregnant and started receiving antenatal care in antenatal care room of Family Guidance Association of Dessie model clinic. In this study, all pregnant women irrespective of their gestational age were included. Since the gestational age of the current pregnancy has no effect on fertility return, all women who are in the first, second and third trimester were eligible and included in this study. Pregnancy status was the main requirement for this study. Whenever they are confirmed pregnant at the time of data collection, they are eligible for the study. Pregnant women who experienced abortion cannot attend antenatal care room rather they attend abortion or delivery room so that they are by default excluded due to this reason.

Result:

Comment 11: Table 1: Where is the age of the participants? Age is a very crucial variable to talk about fertility. Better to show the age distribution of the women, because age is a factor for fertility return.

Response: Thank you dear reviewer for your important comment. We have tried to show the age distribution women on table 1 of our revised manuscript accordingly.

Comment 12: The frequency of sexual intercourse, in the part of others must be reclassified as these are many. Because the women with delayed fertility most likely be in this group.

Response: Thank you. The comment is accepted and addressed accordingly in table 2 of our revised manuscript.

Comment 13: Gestational age must have been included in the obstetrics variables of the study participants to know the proportion of trimesters. If majority are in the second trimester and above, there a possibility to miss those ladies who had abortion and couldn’t be found at ANC which affects the overall proportion of women had return in fertility.

Response: Thank you. We did not assess the gestational age of the women since the gestational age of the current pregnancy it has no effect on fertility return.

Comment 15: Line 162-163: “The proportion of delayed fertility return experienced by pregnant women after discontinuation of any modern contraceptive methods before the current pregnancy was 11.4 % (95% CI; (8-14.4%)).” Here the author must talk about fertility return which is 88.6% not the delay.

Response: Thank you. We acknowledge the problem and amended it accordingly in the result section line188-192.

Comment 16: Line 164-166: this shows that even the fertility rate is very good as 75% conceived within 12 months which is a bit higher that we know from literatures, 70% for DMPA

Response: Thank you. We have amended the conclusion accordingly.

Comment 17: Line 174-175: “a unit increase in age…” was linear regression used? If it is Multivariable why a unit increase is used? And age above what? Or above which age limit?

Response: No, multivariable binary logistic regression was fitted to identify factors associated with delayed fertility return. By the way, continuous variables can be fitted in multivariable logistic regression without categorizing them. However, we have tried to categorize the age of respondents to know which age group is at high risk of having delayed fertility return in our revised manuscript. Accordingly, those aged greater than or equal to 35 years are at high risk of having delayed return in fertility.

Comment 18: Table 4: which age group is at risk of having delayed return in fertility? Because age in an important variable for woman fertility than any other. What is the mean and median age of the women with delayed fertility?

Response: Thank you for your constrictive comment. According to this study, women aged ≥35 years are at risk of having delayed return in fertility as compared to women aged 15-24 years. The mean age of the women with delayed fertility was 29.5 years with SD ± 4.3 years whereas the median age of the women with delayed fertility was 28.5 years with IQR of 4 years.

Discussion

Comment 19: It is very brief and more literatures need to be used.

Response: Thank you for your important comment. We have tried to modify it by searching more literatures.

Comment 20: Age was found to be a significant factor to affect fertility. Age above which limit? <18? >35? A unity increase in age above what? This has to be clear. Because it is known that early age and late age is associated with anovulation and late age and there may be a deal in fertility normally irrespective of contraception use.

Response: Thank you dear reviewer for your important comment. We have tried to categorize respondent’s age. Accordingly, those women aged ≥35 years were more likely experienced delayed fertility return as compared to pregnant women aged 15-24 years.

Comment 21: All the limitations should be stated.

Response: Thank you have tried to put the limitation of the study on page line

Conclusion:

Comment 22: The conclusion and recommendation have to be clear. What is the general conclusion? Is the fertility return high or low? What will be the recommendation? Did the contraception use affect the return in fertility differently in your study area than others? What message do you convey to the public?

Response: Thank you dear reviewer. We have amended conclusion and recommendation section accordingly.

Comment 23: Line 225-226: It is better to talk about the return in fertility than the delay. It is also better to describe that the return in fertility is high in Long-term and reversible contraception (DMPA, IUCD)...which will have a positive impact for the users

Response: Thank you. The comment is accepted and addressed accordingly.

Comment 24: 227-228: Did the authors assess whether the health providers did or didn't counsel the woman about the delay in fertility return when they chose DMPA? This is unfound in the result.

Why? The return in fertility is 75% which is very good. No base for this recommendation.

Response: Thank you for your comment. We did not assess whether or not the health care providers counsel women about the delay in fertility return when they chose DMPA. However in research, it is mandatory to provide recommendation for those concerned stakeholders about the main findings of a study. One of the main findings of our study was the association between using DMPA and delay in fertility return. Although the return in fertility among DMPA users was good (75%), the result of multivariable analysis indicated that pregnant women who used DMPA before the current pregnancy were 4.8 times more likely to experience fertility delay upon discontinuation as compared to women who used IUCD, OCP and implants. Based on this finding, it is mandatory to recommend health care providers to provide detail counseling about the advantage, disadvantage and the side effects (including its effect on fertility return) of each contraceptive methods for the users so that the users can freely choose the best one for themselves .

Reference

Comment 25: Check the references. The journals are not cited appropriately.

Response: Thank you dear reviewer. We have tried to revise the reference accordingly.

Reviewer 3

Comment 1: The article needs to be edited for clarity. There are a lot of phrases that aren’t entirely clear and many details that are not included or are not elaborated upon sufficiently.

Response: Thank you for your important comment. The whole part of the manuscript was revised. In addition, we have tried to put the detail for things that need further elaboration.

Introduction

Comment 2: The introduction section needs to more fully interrogate the existing evidence. The citations indicate several strong articles on the topic of return to fertility after contraceptive use; however, the introduction doesn’t summarize the science in a robust fashion.

Response: Thank you for your suggestion. We have tried to revise the introduction section accordingly.

Comment 3: The paragraph on page 3 (lines 54-56) is quite extreme. The association between impaired fertility and murder are not likely as strong as those between impaired fertility and mental health disorders. This paragraph should be revised to indicate that certain associations of impaired fertility are rare compared to others.

Response: Thank you. We have amended it accordingly.

Material and Methods

Comment 4: Please provide background on FGA Dessie Model Clinic. It’s not clear what this is, who it serves, etc. Where is it? What context? What sorts of people go to this clinic- urban/peri-urban/rural? Stable population or migrating population? Did you collect data at first ANC visit or later ANC visit?

Response: Thank you for your constructive comments. We have tried to provide background information on FGA Dessie Model Clinic in the method section page 4-5 line 83 to 91.

Comment 5: It would be useful to know more about the questionnaire- how many questions? Were the responses open-ended or categorized? If questionnaire derived from previous questionnaires from similar works of literature, it would be useful to cite them.

Response: Thank you dear reviewer for your important comments. A total of 33 socio-demographic, behavioral, contraceptive, obstetric and disease related questions were used to assess fertility return and associated factors among pregnant women attending FGA model clinic of Dessie town. Most of the questions were closed ended questions. However there are some questions with open ended response. These open-ended response questions were categorized based on standards and using previous works of literatures. The questionnaire was derived from previous questionnaires from similar works of literature, we have tried to cite them in our revised manuscript.

Results

Comment 6: It is unclear to me how decisions were made around categorizing Socio-demographic data, notably non-binary behavioral characteristics. I would like confirmation that nearly 18% of the study reports a frequency of sexual intercourse of three times per day- this seems questionable and could skew the results given the association between frequency of intercourse and fertility.

Response: Thank you for your constrictive comment. Non-binary behavioral characteristics were categorized based on standards and based the results of previous literatures. In this study, 17.7% of the pregnant women reports a frequency of sexual intercourse of three times per day before they become pregnant. However, since it is the finding of the study, we have no chance without accepting it as it is.

Comment 7: Please define further the variables. What is history of abortion- are you including spontaneous miscarriages in this definition? What is an irregular menstrual cycle? What would constitute history of medical illness- is it only TB and diabetes or inclusive of other illness? I’m curious about your cutoff for number of births, given that it would be interesting to better understand the distinction between those for whom this is their first pregnancy and those for whom its their second or greater- this is likely related to the sample, but bears noting.

Response: Thank you. In this study, abortion was defined if the pregnancy was terminated before 28 weeks of gestation. It includes both spontaneous and induced. Similarly, a woman said to have irregular menstrual cycle if her cycle is shorter than 21 days or longer than 35 days whereas regular menstrual cycle is a cycle that ranges from 21 to 35 days. History of medical illness constitute only TB and diabetes. These two disease are public health important disease that influence women’s fertility. Evidences suggested that 10 up to 15% of infertility cases among women are as result of TB infection that spread to the reproductive organs (uterus, ovaries and the Fallopian tubes) through bloodstream. Diabetes also plays a significant role in reproductive disorders such as anovulation, menstrual disorders and infertility as it causes obesity. We have re-categorized the cutoff for number of births as “never give birth”, “one birth” and ≥2 births. We have tried to put the operational definition in the method section line 125-131.

Discussion

Comment 8: When citing previous studies, please note the authors, not only the location of the study.

Response: Thank you. It is difficult to put authors for all studies. However, efforts were made to put the authors for studies used in the discussion section accordingly.

Comment 9: Increasing age is associated with decreasing fertility. This is steeped in research. Please cite research on page 16 paragraph on lines 203-209. It currently reads in a speculative manner; however, in reality, these associations are real and documented.

Response: Thank you dear reviewer. We have tried to cite research for it accordingly in the discussion section line 239.

Attachment

Submitted filename: Resposes to reviewers.docx

Click here for additional data file.^{(33.1KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0287440.r003

Decision Letter 1

Janet E Rosenbaum

1 Dec 2022

PONE-D-21-25440R1Fertility return after contraceptive discontinuation and associated factors among women attended Family Guidance Association of Ethiopia Dessie model clinic, Northeast Ethiopia: a cross-sectional studyPLOS ONE

Dear Dr. Damtie,

Please submit your revised manuscript by Jan 15 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
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An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Janet E Rosenbaum, Ph.D.

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #4: (No Response)

Reviewer #5: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #4: Yes

Reviewer #5: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #4: Yes

Reviewer #5: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #4: Yes

Reviewer #5: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #4: Yes

Reviewer #5: Yes

**********

6. Review Comments to the Author

Reviewer #4: This work is interesting but data reported didn't give new informations about fertility return after contraceptive discontinuation.

This fiel has been largely studied and data reported in this work didn't add new informations (1).

1 Girum T, Wasie A. Return of fertility after discontinuation of contraception: a systematic review and meta-analysis. Contracept Reprod Med. 2018 Jul 23;3:9. doi: 10.1186/s40834-018-0064-y. PMID: 30062044; PMCID: PMC6055351.

Reviewer #5: Reviewer comments:

Title: Fertility return after contraceptive discontinuation and associated factors among women attended Family Guidance Association of Dessie model clinic, Northeast Ethiopia: a cross-sectional study

1. Abstract: : Women who use hormonal contraception…..: you have used hormonal contraception the reader will understand you have checked for only hormonal ones !!! Use it at the title also and be sure that when you are recording on the contraception within the text to be hormonal.

2. Abstract line 36: OCP includes combined oral contraception piles and progesterone only piles!!! please refer to it in a more definite way in all the text

3. Introduction, first line: Globally, around 15% of couples experience infertility!!! That is true; the proportion of delayed fertility return among currently pregnant women after discontinuation contraceptive methods was 11.4%in your research!! Do you think that there was any delay in getting pregnant? almost 88% became pregnant within 1 year of attempting pregnancy

4. Introduction line 57-58: These include socio-demographic factors (age) [16]: socio-demographic factors does not means (age ) to put the word between bracket !! either add other factors with the age and this will need many references or delete it

5. Introduction( MMR,FGA) are two abbreviations needs to be proceeded by full description

6. Introduction line 67: . One of the reasons for not using contraceptive methods might be due to fertility delay associated with contraceptive: At introduction you do not add your suggestions for a result!! You may shift it to the discussion section.

7. Page 4 sample size: The sample size was determined by using single population proportion formula by considering the proportion of delayed fertility return as 50%

a. Using 50% reference is a very high percent!! Although there was no research done in this community , in these situations you may use the rate in nearby countries or even any published article on the same purpose

b. A cross sectional study means you will survey in a population about any one whom have used contraception and failed to get pregnant within one year so ideally does not need sample size estimation being a cross sectional study

c. Using single population proportion: which population due mean? Was it at antenatal care unites? Or gynecology outpatient clinic? Or may infertility unit?

8. Result: when I reached the Socio-demographic characteristics then understood that your participants were already pregnant now!!! And still didn’t get the setting of your research!!!!!

9. Page 7, line 131: Ethiopian birr is a local currency which is not understandable for me and the readers!!! Please add to it how much it correspond to using a global currency like American dollar

10. Page 8, line 141: chew chat!! I didn’t understand what it means!! please clarify it in your methods section

11. Page 9, line 144: Pregnant women perform sexual intercourse three times a day and three times a week respectively: what do you mean by this information? They are already pregnant and having intercourse many times does not give you any information about your objectives!!!

12. Page 10, line 156: Four (1%) and 6(1.5%) of pregnant women had a history of Sexual Transmitted Infection (STI) and other medical illness (tuberculosis and diabetic Malthus) :

Although the delayed in getting pregnancy in your sample size was 11% (less than the rate of infertility all over the world (15%), still you have-not excluded whom already infertile from other causes like sexually transmitted disease and uncontrolled diabetes mellitus!! you have to clarify this point or to remove the 4 ladies having other causes for infertility not delay in getting pregnancy after withdrawal of contraception.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #4: No

Reviewer #5: Yes: PROFESSOR SHAHLA KAREEM ALALAF

**********

PLoS One. 2023 Jul 11;18(7):e0287440. doi: 10.1371/journal.pone.0287440.r004

Author response to Decision Letter 1

8 May 2023

Janet E Rosenbaum, Ph.D

Academic Editor, PLOS ONE

RE: Submission ID PONE-D-21-25440 R2 (Fertility return after contraceptive discontinuation and associated factors among women attended Family Guidance Association of Dessie model clinic, Northeast Ethiopia: a cross-sectional study)

Dear Dr. Janet E Rosenbaum,

Please find for your kind consideration the following:

� A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

� A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

� An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Yours Sincerely,

Yitayish Damtie

School of Public Health, Wollo University

Dessie, Ethiopia

Tel:+251943517982

E-mail: yitutile@gmail.com

Point by point responses

Reviewer #4: This work is interesting but data reported didn't give new information’s about fertility return after contraceptive discontinuation. This field has been largely studied and data reported in this work didn't add new information’s (1)

1 Girum T, Wasie A. Return of fertility after discontinuation of contraception: a systematic review and meta-analysis. Contraception Reprod Med. 2018 Jul 23;3:9. doi: 10.1186/s40834-018-0064-y. PMID: 30062044; PMCID: PMC6055351.

Response: Thank you dear reviewer for your comment. Even if return of fertility after discontinuation of contraception has been largely studied and a systematic review and meta-analysis was done at the global level, the field has not been studied yet in Ethiopia. So, this study would have a paramount significance in providing important information for concerned individuals who are working to improve the reproductive health of Ethiopian women.

Reviewer #5:

Title: Fertility return after contraceptive discontinuation and associated factors among women attended Family Guidance Association of Dessie model clinic, Northeast Ethiopia: a cross-sectional study

1. Abstract: Women who use hormonal contraception…... you have used hormonal contraception the reader will understand you have checked for only hormonal ones!!! Use it at the title also and be sure that when you are recording on the contraception within the text to be hormonal.

Response: Thank you dear reviewer for your constructive comment. We have amended it.

2. Abstract line 36: OCP includes combined oral contraception piles and progesterone only piles!!! please refer to it in a more definite way in all the text.

Response: Thank you. As it is indicated in the abstract line 35 and throughout the manuscript, we used the abbreviation OCP to refer oral contraceptive pills which includes both combined oral contraception piles and progesterone only piles.

3. Introduction, first line: Globally, around 15% of couples experience infertility!!! That is true; the proportion of delayed fertility return among currently pregnant women after a discontinuation contraceptive method was 11.4%in your research!! Do you think that there was any delay in getting pregnant? Almost 88% became pregnant within 1 year of attempting pregnancy.

Response: Definitely! Although the figure is not high, 11.4% of currently pregnant women experienced a delayed fertility return after discontinuation of contraceptive methods before they became pregnant.

Response: Many thanks for your comment. We have amended it.

5. Introduction (MMR, FGA) are two abbreviations needs to be proceeded by full description

Response: Thank you for your comment. The full description of FGAE has already written in the abstract section so that we can use the abbreviated form in the subsequent sections. Regarding the abbreviation MMR, we removed it from the introduction due to other reviewer suggestion.

6. Introduction line 67: One of the reasons for not using contraceptive methods might be due to fertility delay associated with contraceptive: At introduction you do not add your suggestions for a result!! You may shift it to the discussion section.

Response: Thank you for your suggestion. We have revised it accordingly.

7. Page 4 sample size: The sample size was determined by using single population proportion formula by considering the proportion of delayed fertility return as 50%

A. Using 50% reference is a very high percent!! Although there was no research done in this community , in these situations you may use the rate in nearby countries or even any published article on the same purpose

Response: Thank you for your important comment. Many scholars recommended using 50% reference for sample size calculation in the case of unknown prevalence since it provides maximum sample size. It is not recommended to use the rate in nearby countries for sample size calculation due to the variation in the concern of government on health and health related issues and health care interventions across countries. In addition, the sample size calculated from studies conducted in nearby countries may not be larger than the sample size calculated using 50% reference for sample size since it provides maximum sample size. The power of the study and precision of the estimate increases with an increase in sample size. As long as it doesn’t affect the power and the precision of the study, it is better to use 50% reference in case of unknown prevalence.

B. A cross sectional study means you will survey in a population about any one whom have used contraception and failed to get pregnant within one year so ideally does not need sample size estimation being a cross sectional study.

Response: Sample size estimation is mandatory for any type of quantitative study including cross-sectional study. This is because if we survey a small number of women, we will not be able to detect an effect and may produce inconclusive result. On the other hand, if we survey large number of women, it may waste scares resources (time, money, manpower etc...). So, determination of a sample size which is an appropriate is crucial to avoid the aforementioned issues.

C. Using single population proportion: which population due mean? Was it at antenatal care unites? Or gynecology outpatient clinic? Or may infertility unit?

Response: Thank you for your comment. It is to mean antenatal care unites.

8. Result: when I reached the Socio-demographic characteristics then understood that your participants were already pregnant now!!! And still didn’t get the setting of your research!!!!!

Response: Really! Our study participants were women who are pregnant at the time of study. The aim of our study was to assess whether fertility was returned (whether women became pregnant) within 12 months of contraceptive discontinuation or not and to determine factors for those women who experience delayed in return of fertility after contraceptive discontinuation. Fertility return was defined if conception occurred within 12 months following discontinuation of any modern contraceptive methods. On the other hand, delayed fertility return was defined if conception occurred after 12 months following discontinuation of any modern contraceptive methods. So to achieve our objective, study participants should be pregnant women.

9. Page 7, line 131: Ethiopian birr is a local currency which is not understandable for me and the readers!!! Please add to it how much it correspond to using a global currency like American dollar

Response: Thank you for your important comment. We have tried to change it to American dollar.

10. Page 8, line 141: chew khat!! I didn’t understand what it means!! Please clarify it in your methods section.

Response: Thank you. To make it clear, Khat is a fresh green leave plant native to eastern Africa and the Arabian Peninsula. In 1980, WHO classified it as an illicit substance due to the potential for psychological dependence. Khat contains a psycho-active ingredient cathinone which is said to cause excitement, and euphoria. Its regular consumption negatively impacts the human central nervous system, systemic blood pressure, psychological health and reproductive system causing reproductive toxicity and sexual dysfunction. We have tried to clarify it in the method section as well.

Response: Yes, this study was conducted among women who are already pregnant. However, we used frequency of sexual intercourse as a factor to assess how often they performed sexual intercourse before they become pregnant since frequency of sexual intercourse is an important factor for the occurrence of pregnancy (fertility return). It is known that women who perform sexual intercourse three times a day, three times a week, three times a month and three times a year have no equal chance of becoming pregnant.

12. Page 10, line 156: Four (1%) and 6(1.5%) of pregnant women had a history of Sexual Transmitted Infection (STI) and other medical illness (tuberculosis and diabetic Malthus). Although the delayed in getting pregnancy in your sample size was 11% (less than the rate of infertility all over the world (15%), still you have-not excluded whom already infertile from other causes like sexually transmitted disease and uncontrolled diabetes mellitus!! you have to clarify this point or to remove the 4 ladies having other causes for infertility not delay in getting pregnancy after withdrawal of contraception.

Response: Thank you for your comment. Our study participants were women who are pregnant at the time of study. Infertility could not be an issue for our study participants since they are already pregnant. Studies suggested that having STI and other medical illness like Tuberculosis and diabetic Malthus can delay pregnancy or may causes infertility if they are left untreated. Due to these, we want to test their statistical significance association with delay in getting pregnancy.

Attachment

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PLoS One. doi: 10.1371/journal.pone.0287440.r005

Decision Letter 2

Janet E Rosenbaum

6 Jun 2023

Fertility return after hormonal contraceptive discontinuation and associated factors among women attended Family Guidance Association of Ethiopia Dessie model clinic, Northeast Ethiopia: a cross-sectional study

PONE-D-21-25440R2

Dear Dr. Damtie,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. 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.

Kind regards,

Janet E Rosenbaum, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #5: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #5: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #5: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #5: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #5: Yes

**********

6. Review Comments to the Author

Reviewer #5: The correspond author responded to the previous comments were adequately addressed. The article is suitable now for publication

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #5: Yes: SHAHLA KAREEM ALALAF

**********

PLoS One. doi: 10.1371/journal.pone.0287440.r006

Acceptance letter

Janet E Rosenbaum

3 Jul 2023

PONE-D-21-25440R2

Dear Dr. Damtie:

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.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Janet E Rosenbaum

Academic Editor

PLOS ONE

Associated Data

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

Supplementary Materials

S1 Table. STROBE checklist.

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Data Availability Statement

All relevant data are within the paper and its Supporting Information files.

[pone.0287440.ref001] 1.Olson DJ, Piller A. Ethiopia: an emerging family planning success story. Studies in family planning 2013; 44(4):445–459. doi: 10.1111/j.1728-4465.2013.00369.x [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref002] 2.USAID. Update on family planning in Sub-Saharan Africa. Repositioning family planning: guidelines for advocacy action. Washington: Academy for Educational Development; 2009. [Google Scholar]

[pone.0287440.ref003] 3.Smith R, Ashford L, Gribble J, Clifton D: Family planning saves lives. Washington DC: Population Reference Bureau; 2009, 5. [Google Scholar]

[pone.0287440.ref004] 4.United Nations DoE, Social Affairs PD: Contraceptive Use by Method 2019: Data Booklet (ST/ESA/SER. A/435). In.: United Nations, Department of Economic and Social Affairs, Population Division; 2019. [Google Scholar]

[pone.0287440.ref005] 5.Sedgh G, Hussain R: Reasons for contraceptive nonuse among women having an unmet need for contraception in developing countries. Studies in family planning 2014, 45(2):151–169. [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref006] 6.Central Statistical Agency Addis Ababa Ethiopia. Demographic and Health Survey 2016. Federal Democratic Republic of Ethiopia; 2017. [Google Scholar]

[pone.0287440.ref007] 7.Campbell M, Sahin‐Hodoglugil NN, Potts M: Barriers to fertility regulation: a review of the literature. Studies in family planning 2006, 37(2):87–98. doi: 10.1111/j.1728-4465.2006.00088.x [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref008] 8.Gueye A, Speizer IS, Corroon M, Okigbo CC: Belief in family planning myths at the individual and community levels and modern contraceptive use in urban Africa. International Perspectives on Sexual and reproductive health 2015, 41(4):191. doi: 10.1363/4119115 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0287440.ref009] 9.Diamond-Smith N, Campbell M, Madan S: Misinformation and fear of side-effects of family planning. Culture, health & Sexuality 2012, 14(4):421–433. doi: 10.1080/13691058.2012.664659 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref010] 10.Okenwa L, Lawoko S, Jansson B: Contraception, reproductive health, and pregnancy outcomes among women exposed to intimate partner violence in Nigeria. The European Journal of Contraception & Reproductive Health Care 2011, 16(1):18–25. doi: 10.3109/13625187.2010.534515 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref011] 11.Zhu H, Lei H, Huang W, Fu J, Wang Q, Shen L, et al. : Fertility in older women following removal of long-term intrauterine devices in the wake of a natural disaster. Contraception 2013, 87(4):416–420. doi: 10.1016/j.contraception.2012.11.002 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref012] 12.Delbarge W, Batar I, Bafort M, Bonnivert J, Colmant C, Dhont M, et al. : Return to fertility in nulliparous and parous women after removal of the GyneFix® intrauterine contraceptive system. The European Journal of Contraception & Reproductive Health Care 2002, 7(1):24–30. [PubMed] [Google Scholar]

[pone.0287440.ref013] 13.Issa AA, Amr MF: Fertility after removal of intrauterine contraceptive devices. Current therapeutic research 1998, 59(4):257–261. [Google Scholar]

[pone.0287440.ref014] 14.Mansour D, Gemzell-Danielsson K, Inki P, Jensen JT: Fertility after discontinuation of contraception: a comprehensive review of the literature. Contraception 2011, 84(5):465–477. doi: 10.1016/j.contraception.2011.04.002 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref015] 15.Girum T, Wasie A: Return of fertility after discontinuation of contraception: a systematic review and meta-analysis. Contraception and reproductive medicine 2018, 3(1):1–9. doi: 10.1186/s40834-018-0064-y [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0287440.ref016] 16.Jacobstein R: Long-acting and permanent contraception: an international development, service delivery perspective. Journal of Midwifery & women’s Health 2007, 52(4):361–367. doi: 10.1016/j.jmwh.2007.01.001 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref017] 17.Kulier R, O’Brien P, Helmerhorst FM, Usher‐Patel M, d’Arcangues C: Copper containing, framed intra‐uterine devices for contraception. Cochrane Database of systematic reviews 2007(4). doi: 10.1002/14651858.CD005347.pub3 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref018] 18.Brief BP: Prevention of Postpartum Hemorrhage in Rural Ethiopia. 2012. [Google Scholar]

[pone.0287440.ref019] 19.Gayatri M, Utomo B, Budiharsana M: How soon can you expect to get pregnant after discontinuing the reversible contraceptive method? A survival analysis of the 2017 Indonesia demographic and health survey data. EXECUTIVE EDITOR 2020, 11(01):310. [Google Scholar]

[pone.0287440.ref020] 20.Barden-O’Fallon J, Speizer IS, Calhoun LM, Moumouni NA: Return to pregnancy after contraceptive discontinuation to become pregnant: a pooled analysis of West and East African populations. Reproductive Health 2021, 18(1):1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0287440.ref021] 21.Shearman R: Amenorrhea after treatment with oral contraceptives. Lancet (London, England) 1966, 2(7473):1110. doi: 10.1016/s0140-6736(66)92197-0 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref022] 22.Vessey M, Wright N, McPherson K, Wiggins P: Fertility after stopping different methods of contraception. Br Med J 1978, 1(6108):265–267. doi: 10.1136/bmj.1.6108.265 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0287440.ref023] 23.Linn S, Schoenbaum SC, Monson RR, Rosner B, Ryan KJ: Delay in conception for former’pill’users. Jama 1982, 247(5):629–632. [PubMed] [Google Scholar]

[pone.0287440.ref024] 24.Harlap S, Baras M: Conception-waits in fertile women after stopping oral contraceptives. International Journal of Fertility 1984, 29(2):73–80. [PubMed] [Google Scholar]

[pone.0287440.ref025] 25.Chasan-Taber L, Willett WC, Stampfer MJ, Spiegelman D, Rosner BA, Hunter DJ, et al. : Oral contraceptives and ovulatory causes of delayed fertility. American journal of Epidemiology 1997, 146(3):258–265. doi: 10.1093/oxfordjournals.aje.a009261 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref026] 26.Castle S: Factors influencing young Malians’ reluctance to use hormonal contraceptives. In.: Wiley Online Library; 2003. [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref027] 27.Ochako R, Mbondo M, Aloo S, Kaimenyi S, Thompson R, Temmerman M, et al. : Barriers to modern contraceptive methods uptake among young women in Kenya: a qualitative study. BMC public health 2015, 15(1):1–9. doi: 10.1186/s12889-015-1483-1 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0287440.ref028] 28.Burke H, Ambasa-Shisanya C: Qualitative study of reasons for discontinuation of injectable contraceptives among users and salient reference groups in Kenya. African Journal of reproductive health 2011, 15(2). [PubMed] [Google Scholar]

[pone.0287440.ref029] 29.Fotherby K, Yong-En S, Howard G, Elder M, Muggeridge J: Return of ovulation and fertility in women using norethisterone oenanthate. Contraception 1984, 29(5):447–455. doi: 10.1016/0010-7824(84)90018-0 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref030] 30.Pardthaisong T, Gray R, Mcdaniel E: Return of fertility after discontinuation of depot medroxyprogesterone acetate and intra-uterine devices in Northern Thailand. The Lancet 1980, 315(8167):509–512. doi: 10.1016/s0140-6736(80)92765-8 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref031] 31.Organization WH: Family planning: a global handbook for providers: 2011 update: evidence-based guidance developed through worldwide collaboration. 2011. [Google Scholar]

[pone.0287440.ref032] 32.Vessey MP, Smith M, Yeates D: Return of fertility after discontinuation of oral contraceptives: influence of age and parity. Br J Fam Plann 1986, 11(4):120–124. [Google Scholar]

[pone.0287440.ref033] 33.Buck GM, Sever LE, Batt RE, Mendola P: Life-style factors and female infertility. Epidemiology 1997:435–441. doi: 10.1097/00001648-199707000-00015 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref034] 34.Stoddard AM, Xu H, Madden T, Allsworth JE, Peipert JF: Fertility after intrauterine device removal: a pilot study. The European Journal of Contraception & Reproductive Health Care 2015, 20(3):223–230. doi: 10.3109/13625187.2015.1010639 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0287440.ref035] 35.Wallach EE, Huggins GR, Cullins VE: Fertility after contraception or abortion. Fertility and sterility 1990, 54(4):559–573. doi: 10.1016/s0015-0282(16)53808-4 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref036] 36.Farrow A, Hull M, Northstone K, Taylor H, Ford W, Golding J: Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception. Human Reproduction 2002, 17(10):2754–2761. doi: 10.1093/humrep/17.10.2754 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref037] 37.Gayatri M, Utomo B, Budiharsana M, Dasvarma G: Pregnancy resumption following contraceptive discontinuation: Hazard survival analysis of the Indonesia Demographic and Health Survey Data 2007, 2012 and 2017. Plos one 2022, 17(2):e0264318. doi: 10.1371/journal.pone.0264318 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0287440.ref038] 38.Tadesse E: Return of fertility after an IUD removal for planned pregnancy: a six-year prospective study. East African medical journal 1996, 73(3):169–171. [PubMed] [Google Scholar]

[pone.0287440.ref039] 39.Buckshee K, Chatterjee P, Dhall G, Hazra M, Kodkany B, Lalitha K, et al. : Return of fertility following discontinuation of norplantR-II subdermal implants: ICMR task force on hormonal contraception. Contraception 1995, 51(4):237–242. [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref040] 40.Sivin I, Stern J, Diaz S, Pavéz M, Alvarez F, Brache V, et al. : Rates and outcomes of planned pregnancy after use of Norplant capsules, Norplant II rods, or levonorgestrel-releasing or copper TCu 380Ag intrauterine contraceptive devices. American Journal of obstetrics and Gynecology 1992, 166(4):1208–1213. doi: 10.1016/s0002-9378(11)90607-3 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref041] 41.Hook EB: Rates of chromosome abnormalities at different maternal ages. Obstetrics and gynecology 1981, 58(3):282–285. [PubMed] [Google Scholar]

[pone.0287440.ref042] 42.Capezzuoli T, Vannuccini S, Fantappiè G, Orlandi G, Rizzello F, Coccia ME, et al. : Ultrasound findings in infertile women with endometriosis: evidence of concomitant uterine disorders. Gynecological Endocrinology 2020, 36(9):808–812. doi: 10.1080/09513590.2020.1736027 [DOI] [PubMed] [Google Scholar]

[pone.0287440.ref043] 43.Yland JJ, Bresnick KA, Hatch EE, Wesselink AK, Mikkelsen EM, Rothman KJ, et al. : Pregravid contraceptive use and fecundability: prospective cohort study. bmj 2020, 371. doi: 10.1136/bmj.m3966 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0287440.ref044] 44.Pardthaisong T: Return of fertility after use of the injectable contraceptive Depo Provera: updated data analysis. Journal of Biosocial Science 1984, 16(1):23–34. doi: 10.1017/s0021932000014760 [DOI] [PubMed] [Google Scholar]

PERMALINK

Fertility return after hormonal contraceptive discontinuation and associated factors among women attended Family Guidance Association of Ethiopia Dessie model clinic, Northeast Ethiopia: A cross-sectional study

Yitayish Damtie

Bereket Kefale

Mastewal Arefaynie

Melaku Yalew

Bezawit Adane

Roles

Abstract

Background

Methods

Result

Conclusions

Introduction

Material and methods

Study area, study design, and participants

Sample size and sampling procedure

Data collection procedures and measurements

Statistical analysis

Ethical approval

Results

Socio-demographic characteristics

Table 1. Socio-demographic characteristics of pregnant women who attended FGAE Dessie model clinic, Northeast Ethiopia, 2019.

Behavioral characteristics

Table 2. Behavioral characteristics of pregnant women who attended FGAE Dessie model clinic, Northeast Ethiopia, 2019.

Contraceptive, obstetric, and disease-related characteristics

Table 3. Contraceptive, obstetric, and disease-related characteristics of pregnant women attended FGA Dessie model clinic, Northeast Ethiopia, 2019.

The proportion of fertility return

Factors associated with delayed fertility return

Table 4. Factors associated with delayed fertility return after hormonal contraceptive discontinuation among pregnant women attended FGAE Dessie model clinic, Northeast Ethiopia, 2019.

Discussion

Conclusion

Supporting information

Acknowledgments

List of abbreviations

Data Availability

Funding Statement

References

Decision Letter 0

Janet E Rosenbaum

Roles

Author response to Decision Letter 0

Decision Letter 1

Janet E Rosenbaum

Roles

Author response to Decision Letter 1

Decision Letter 2

Janet E Rosenbaum

Roles

Acceptance letter

Janet E Rosenbaum

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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