Abstract
Objectives
We determined if the time interval between two ovulation induction intrauterine artificial insemination (IUI) treatment cycles should be extended by one or more natural menstrual cycles in patients undergoing successive cycles of ovulation stimulation, and whether this affects clinical pregnancy rate (CPR).
Design
This study was conducted on infertility patients treated under the ovulation induction programme IUI in a large reproductive centre in China. Study participants were assigned into continuous and discontinuous groups. Differences in baseline clinical pregnancy and abortion rates were compared between the groups. A multivariate logistic model was used to evaluate the effects of time interval on clinical pregnancy outcomes.
Setting
Reproductive Centre of Maternal and Child Health Hospital of Lianyungang city.
Interventions
None.
Primary and secondary outcome measures
The primary outcome measure was CPR, the secondary outcome measure was the abortion rate.
Results
A total of 550 IUI treatment cycles involving 275 couples were included in this study. Differences in CPR and abortion rate between the groups were not significant (20.5% vs 21.9% and 27.8% vs 22.0%, p≥0.05). Stratified analyses based on infertility factors did not reveal any significant differences in pregnancy and abortion rates between the groups (p≥0.05). Multivariate analysis showed that increased endometrial thickness correlates with CPR (OR 1.205, 95% CI 1.05 to 1.384, p=0.008). Compared with primary infertility, secondary infertility significantly correlated with improved CPR (OR 2.637, 95% CI 1.313 to 5.298, p=0.006). The effects of time interval between the first two ovulation induction IUI treatment cycles on clinical pregnancy were not significant (OR 1.007, 95% CI 0.513 to 1.974, p=0.985).
Conclusions
Longer time intervals between the first two ovulation induction IUI treatment cycles did not significantly improve CPR. Therefore, in the absence of clear clinical indications, it may not be necessary to deliberately prolong the interval between two ovulation induction IUI treatment cycles.
Keywords: genitourinary medicine, reproductive medicine, subfertility
Strengths and limitations of this study.
This is the first study to explore the effects of one or more prolonged natural menstrual cycles on pregnancy outcomes in intrauterine artificial insemination.
The number of cases included is large.
Data were obtained from a reliable clinical database of a large medical institution.
There were no subgroup analyses in the discontinuous group according to the delay time range, such as 1, 2, 3 or more natural cycles before the second treatment cycle.
This study was conducted in a single centre, therefore, the applicability of our conclusions to other populations maybe limited.
Introduction
Intrauterine insemination (IUI) is commonly used to enhance the success rate of pregnancy in fertility clinics. This technique is less likely to incur damage to the uterus as well as ovaries and is highly affordable.1 IUI involves identifying excellent sperms after removal of seminal plasma and transcervically introducing the sperms into the uterine cavity. However, compared with in vitro fertilisation and embryo transfer (IVF-ET), the successful pregnancy rate of IUI is low. Therefore, for most patients, multiple attempts are necessary before successful pregnancy. This necessitates the need to develop novel strategies for improving the success rate of IUI treatments. The number of studies investigating if frozen ET should be delayed during IVF-ET treatment have gradually increased, but they have reported inconsistent conclusions. Some studies report that extending the interval between two IVF treatments does not significantly improve the pregnancy rate,2–5 while other studies have come to the opposite conclusion, favouring a longer interval between IVF cycles as an effective way for increasing the clinical pregnancy rates (CPRs).6 7 Currently, it has not been conclusively determined whether rest after IUI failure is beneficial. Thus, to inform clinical applications of IUI, we determined if the time interval between two ovulation induction IUI treatment cycles influences CPRs.
Materials and methods
Study population and design
We retrospectively reviewed all IUI cases at the Reproductive Medicine Centre of Lianyungang Maternal and Child Health Hospital from 1 January 2017 to 31 December 2019. Indications for IUI treatment included tubal problems, unexplained infertility, infertility due to cervical factors, ovulation disorders (refer to Rotterdam standard),8 and infertility due to mild or moderately low male fertility (refer to WHO standard).9 This study included patients who had received at least two ovulation induction cycle IUI treatments. To avoid including cases with multiple repeat cycles involving the same couple, only the first two ovulation induction IUI treatment cycles were included per couple. To minimise the impacts of confounding factors associated with long intervals and advancing age on pregnancy outcomes, the interval between the first two ovulation induction IUI treatment cycles was less than 180 days. Patient data were obtained from the clinical database and statistical analyses performed with reference to the above standards.
IUI treatment procedures
Ovulation induction therapy
For patients with sparse menstruation, natural cycle follicular dysplasia, ovulation disorders or previous natural cycle IUI treatment but not pregnant, ovulation induction treatment was performed. Prior to insemination operation, patients were given oralletrozole (LE) combined with human menopausal gonadotropin (HMG) for ovulation induction therapy. Namely, ovulation induction IUI treatment. After 48 hours, the number and diameter of follicles were measured by transvaginal ultrasonography, and the maturation degree of ovarian follicles evaluated by assessing luteinising hormone levels in blood and urine. Based on examination results, the dose of LE combined with HMG was timely adjusted to control the number of dominant follicles (diameter ≥14 mm) to within 3, checking every other day after that. When any follicle reached 18 mm in diameter, 5000 IU of human chorionic gonadotropin (hCG) was injected. After injection, b-mode ultrasound was performed to check ovulation and prepare for insemination. In cases of non-ovulation, subcutaneous injection of triprerelin hydrochloride 0.1 mg was performed to promote ovulation. If there is still no ovulation, artificial insemination was judged to have failed.
Endometrial thickness and type monitoring
On the insemination day, endometrial thickness was measured by vaginal ultrasound and classified according to ultrasonic characteristics. Endometrial thickness is the maximum thickness of the upper endometrium measured on the longitudinal section of the uterus perpendicular to the uterine cavity line. Gonen classification was used to classify the endometrium into three types. Type A: typical trilinear sign, type B: isolated echo in the middle, type C: homogeneous strong echo with no midline echo of the uterine cavity. This monitoring was repeated for each cycle of each patient.
Semen collection and treatment
Generally, patients were required to ejaculate once, 2–7 days before insemination and to avoid sex in this period. This was done to ensure semen quality on the insemination day. On the insemination day, male partners were asked to collect semen in a private room next to the laboratory to minimise the adverse effects of fluctuating ambient temperatures on sperm quality. Semen samples were collected by masturbation and purified by density gradient centrifugation after liquefaction for 30 min at 37°C. Sperm density, viability and volume were determined before and after density gradient centrifugation.
Timing of insemination
In ordinary circumstances, insemination was scheduled for 24–36 hours after hCG injection.
Luteal support and follow-up
Immediately after insemination, patients began oral progesterone for luteal support therapy. On day 14 after artificial insemination, serum β-HCG levels were used for pregnancy detection. For negative pregnancy tests, luteal support therapy was immediately stopped. For pregnancy positive patients (β-HCG levels >20 IU/L), luteal support therapy was continued until 10–12 weeks of gestation.
Grouping method
Systematic database searches were conducted to determine the date of first insemination operation, the date of last menstruation before the second ovulation induction IUI treatment cycle and the start date of second ovulation induction cycle IUI treatment cycle. First, the time interval between the first two ovulation induction IUI treatment cycles was ensured to be less than 180 days. Then, groups were divided according to time intervals between the date of first insemination operation and the date of last menstruation before the second ovulation induction IUI treatment. At 14 days after the first insemination operation, serum HCG levels were measured to determine pregnancy. None of the patients in this study were pregnant after the first IUI, therefore, luteal support therapy was immediately stopped. If the patient does not receive the next ovulation induction IUI treatment at this time, but performs the ovulation induction IUI treatment after one or more natural menstrual cycles, because the normal menstrual level of women was defined as a spontaneous cycle length of 21–35 days,5 then the last menstrual date before the second ovulation induction IUI treatment is at least 35 days (14+21) from the date of first insemination operation. This case was defined as the discontinuous treatment group (≥35 days). If there was less than 35 days between the last menstrual date before the second ovulation induction IUI treatment and the date of first insemination operation, then, this indicated that the patient had immediately began the next ovulation induction IUI treatment without experiencing a natural menstrual cycle, which was defined as the continuous treatment group (≤34 days; figure 1).
Figure 1.
Grouping method. In the continuous treatment group the time interval between the date of first insemination operation and the last menstrual date before the second ovulation induction IUI treatment was ≤34 days. In the discontinuous treatment group the time interval between the date of first insemination operation and the last menstrual date before the second ovulation induction cycle IUI treatment was ≥35 days. IUI, intrauterine insemination.
Primary and secondary outcome measures
The primary outcome measure was CPR the second ovulation induction IUI treatment cycle. Secondary outcomes included abortion rates. Clinical pregnancy was indicated by the presence of an intrauterine gestation sac at 7 weeks of gestation, as revealed by transvaginal ultrasound. Pregnancy termination due to any cause after confirmed clinical pregnancy was considered as abortion. Abortion rate was determined as: number of abortion cycles/number of clinical pregnancy cycles.
Patient and public involvement
No patient involved.
Statistical analysis
All statistical analyses were performed using SPSS V.26.0 (IBM). First, data were tested for normality using Shapiro-Wilk’s statistics. Values are expressed as mean±SD Categorical variables are expressed as percentages (n%). Comparisons between groups were performed using the χ2 or Fisher’s exact tests. Given that this retrospective study may have included numerous unmeasured confounders, binary logistic regression analysis was used to evaluate the relationship between IUI interval and clinical pregnancy and to estimate the OR with a corresponding bilateral 95% CI. The confounding factors included age, infertility duration, infertility type, female body mass index (BMI), endometrial classification, endometrial thickness, semen volume before treatment, sperm density before treatment, percentage of forward motile sperms before treatment, sperm density after treatment, percentage of forward motile sperms after treatment and the interval between two IUI cycles. A p≤0.05 was considered statistically significant.
Results
Basic information
A total of 1358 treatment cycles of IUI were conducted between January 2017 and December 2019. Among them, 722 ovulation induction IUI treatment cycles were included in this study. Since we only included the first two ovulation induction IUI treatment cycles, 160 redundant treatment cycles of IUI were excluded. Next, patients whose time interval between the first IUI and second IUI was more than 180 days were excluded. Finally, 550 ovulation induction IUI treatment cycles involving 275 couples were included in this study (figure 2). Among them, 374 (68.0%) ovulation induction IUI treatment cycles were classified in the continuous treatment group, while 176 (32.0%) were classified in the discontinuous treatment group. Baseline characteristics for patients in the two groups were comparable (p>0.05, table 1).
Figure 2.
Flow chart of the study. Flow chart of the study. IUI, intrauterine insemination.
Table 1.
Demographic characteristics of continuous treatment group and discontinuous treatment group
| Variable | Continuous treatment group n=187 | Discontinuous treatment group n=88 | P value |
| Male age (years) | 30.44±3.93 | 30.70±3.88 | 0.600 |
| Female age (years) | 29.34±3.42 | 29.50±4.12 | 0.739 |
| Type of infertility n (%) | |||
| Primary infertility | 132 (70.6) | 56 (63.6) | 0.248 |
| Secondary infertility | 55 (29.4) | 32 (36.4) | |
| Female BMI | 24.19±3.88 | 24.92±3.51 | 0.135 |
| Endometrial thickness (mm) | 11.37±2.40 | 11.04±2.45 | 0.287 |
| Endometrial classification, n (%) | |||
| A | 111 (59.4) | 51 (58.0) | 0.461 |
| B | 71 (38.0) | 32 (36.4) | |
| C | 5 (2.7) | 5 (5.7) | |
| Semen volume before treatment (mL) | 3.10±1.34 | 3.19±1.29 | 0.592 |
| Sperm density before treatment (×106 /mL) | 81.23±55.25 | 79.95±56.30 | 0.859 |
| Percentage of forward motile sperm before treatment (%) | 48.43±13.78 | 47.65±11.20 | 0.643 |
| Sperm density after treatment (×106 /mL) | 86.98±55.96 | 83.72±53.40 | 0.648 |
| Percentage of forward motile sperm after treatment (%) | 97.70±3.54 | 97.66±3.82 | 0.939 |
| Duration of infertility n (%) | |||
| ≤2 years | 64 (34.2) | 29 (33.0) | 0.295 |
| 2–5 years | 89 (47.6) | 36 (40.9) | |
| ＞5 years | 34 (18.2) | 23 (26.1) | |
| Infertility factorsn, n (%) | |||
| Ovulation disorders | 92 (49.2) | 42 (47.7) | 0.830 |
| Unexplained infertility | 48 (25.7) | 24 (27.3) | |
| Tubal problems | 21 (11.2) | 9 (10.2) | |
| Male factor | 11 (5.9) | 8 (9.1) | |
| Cervical factors | 15 (8.0) | 5 (5.7) | |
BMI, body mass index.
Pregnancy outcomes
Differences in clinical pregnancy and abortion rates between the continuous and discontinuous treatment groups were not significant (21.9% vs 20.5%; p=0.782% and 22.0% vs 27.8%; p=0.628, respectively, table 2).
Table 2.
Pregnancy outcomes in continuous and discontinuous treatment groups
| Continuous treatment group n=187 | Discontinuous treatment group n=88 | χ2 value | P value | |
| Clinical pregnancy rates n (%) | 41 (21.9) | 18 (20.5) | 0.077 | 0.782 |
| Abortion rate n (%) | 9 (22.0) | 5 (27.8) | 0.235 | 0.628 |
The study population was also stratified according to infertility factors. With regards to infertility factors, differences between pregnancy outcomes under different infertility factors were insignificant (p≥0.05, tables 3 and 4).
Table 3.
Comparison of clinical pregnancy rate between two groups under different infertility factors
| Clinical pregnancy rates n (%) | Continuous treatment group n=41 | Discontinuous treatment group n=18 | χ2 value | P value |
| Ovulation disorders | 25 (27.2) | 11 (26.2) | 0.014 | 0.905 |
| Unexplained infertility | 9 (18.8) | 1 (4.2) | 1.756 | 0.185 |
| Tubal problems | 5 (23.8) | 1 (11.1) | Fisher | 0.637 |
| Male factor | 2 (18.2) | 3 (37.5) | Fisher | 0.603 |
| Cervical factors | 0 (0) | 2 (40.0) | Fisher | 0.053 |
Fisher: Fisher’s exact probability test.
Table 4.
Comparison of abortion rate between two groups under different infertility factors
| Abortion rate n (%) | Continuous treatment group n=9 | Discontinuous treatment group n=5 | χ2 value | P value |
| Ovulation disorders | 5 (20.0) | 3 (27.3) | Fisher | 0.678 |
| Unexplained infertility | 2 (22.2) | 0 (0) | Fisher | 1 |
| Tubal problems | 1 (20.0) | 1 (100) | Fisher | 0.333 |
| Male factor | 1 (50.0) | 0 (0) | Fisher | 0.400 |
| Cervical factors | 0 (0) | 1 (100) |
Fisher: Fisher’s exact probability test.
Multivariate analysis
Age (male and female), infertility duration, infertility type, female BMI, endometrial classification, endometrial thickness, semen volume before treatment, sperm density before treatment, percentage of forward motile sperms before treatment, sperm density after treatment, percentage of forward motile sperms after treatment, infertility factors and the interval between two IUI cycles were included in the binary logistic regression analysis. Increased endometrial thickness was significantly correlated with higher CPRs (OR 1.217, 95% CI 1.056 to 1.401, p=0.006). Compared with primary infertility, secondary infertility significantly correlated with better CPRs (OR 2.917, 95% CI 1.421 to 5.988, p=0.004). The impact of time interval between the first two ovulation induction IUI treatment cycles on clinical pregnancy was not significant (OR 0.984, 95% CI 0.495 to 1.957, p=0.964, table 5).
Table 5.
Relationship between the time interval between two ovulation induction IUI trearment cycles and clinical pregnancy after adjusting for confounding factors
| Variable | Control group | B value | OR value | OR 95% CI | P value |
| Time interval | |||||
| Discontinuous | Continuous | −0.016 | 0.984 | 0.495 to 1.957 | 0.964 |
| Male age (years) | −0.026 | 0.974 | 0.849 to 1.117 | 0.708 | |
| Female age (years) | 0.016 | 1.016 | 0.876 to 1.179 | 0.831 | |
| Type of infertility | |||||
| Secondary infertility | Primary infertility | 1.07 | 2.917 | 1.421 to 5.988 | 0.004 |
| Female BMI | 0.059 | 1.061 | 0.972 to 1.159 | 0.186 | |
| Endometrial thickness (mm) | 0.196 | 1.217 | 1.056 to 1.401 | 0.006 | |
| Semen volume before treatment (mL) | −0.224 | 0.799 | 0.615 to 1.039 | 0.095 | |
| Sperm density before treatment (×106 /mL) | −0.004 | 0.996 | 0.987 to 1.004 | 0.318 | |
| Percentage of forward motile sperm before treatment (%) | −0.005 | 0.995 | 0.97 to 1.021 | 0.73 | |
| Sperm density after treatment (×106 /mL) | 0.004 | 1.004 | 0.995 to 1.013 | 0.419 | |
| Percentage of forward motile sperm after treatment (%) | 0.041 | 1.042 | 0.937 to 1.157 | 0.448 | |
| Duration of infertility | |||||
| 2–5 years | ≤2 years | 0.298 | 1.347 | 0.668 to 2.715 | 0.405 |
| ＞5 years | ≤2 years | −0.836 | 0.433 | 0.159 to 1.185 | 0.103 |
| Endometrial classification, n (%) | |||||
| B | A | −0.694 | 0.5 | 0.243 to 1.026 | 0.059 |
| C | A | 0.409 | 1.505 | 0.312 to 7.254 | 0.61 |
| Infertility factors | |||||
| Ovulation disorders | Cervical factors | 1.091 | 2.978 | 0.585 to 15.175 | 0.189 |
| Unexplained infertility | Cervical factors | 0.143 | 1.153 | 0.205 to 6.475 | 0.871 |
| Tubal problems | Cervical factors | 0.568 | 1.765 | 0.285 to 10.939 | 0.541 |
| Male factor | Cervical factors | 1.224 | 3.4 | 0.504 to 22.941 | 0.209 |
Adjustment factors include: Female age, male age, infertility duration, infertility type, female BMI, endometrial classification, endometrial thickness, semen volume before treatment, sperm density before treatment, percentage of forward motile sperm before treatment, sperm density after treatment, percentage of forward motile sperm after treatment, infertility factors and the time interval between two ovulation induction IUI trearment cycles.
BMI, body mass index; IUI, intrauterine insemination.
Discussion
In this study, we found that spacing one or more natural menstrual cycles before the second ovulation induction IUI treatment did not significantly improve pregnancy outcomes.
Human IUI, which was first reported by Guttmacher10 and Kohlberg,11 12 has a history of nearly 60 years and its awareness has gradually increased. Like other assisted reproductive technologies, IUI is aimed at enhancing the pregnancy rates and minimising risks. However, relative to IVF-ET, pregnancy rates after IUI remain low.13 The IUI pregnancy rate may be influenced by factors such as female age, duration of infertility, history of pelvic diseases (including pelvic inflammatory disease, surgery and endometriosis) and serious male factors (including severe oligospermia, severe asthenospermia and teratospermia). However, IUI is effective for infertility resulting from cervical causes, unexplained infertility and ovulation disorders.14 Depression and anxiety are more common in infertile women than in fertile women.15 The European society for human reproduction and embryology reported that despite advances in IVF technology, the increase in ET rates have not been significant, suggesting that in addition to physiological factors, other factors may influence pregnancy outcomes after IVF. Indeed, negative emotions like stress, anxiety, and depression affect clinical pregnancy and live birth rates after IVF-ET. The more distressed women are before and during treatment, the lower the pregnancy rate.16–21
However, to our knowledge, the relationship between the interval between two IUIs and pregnancy outcomes has not been evaluated, and past studies have mainly focused on IVF-ET. Horowitz et al22 determined whether frozen ET should be performed again after failure of fresh IVF cycles and whether it can be performed immediately in the next menstrual cycle. They found that pregnancy outcomes of immediate and delayed frozen ETs in the natural cycle were comparable. Delayed frozen ETs did not improve reproductive outcomes after failure of fresh cycle IVF, consistent with findings by previous studies.23 24 Reichman et al25 evaluated the therapeutic implications of interval treatment in IVF cycles using a continuous GnRH-antagonist regimen. Among the the 721 ovulation induction IUI treatment cycles included in Reichman’s study, 164 cases began another ovulation induction IUI treatment cycle after waiting for one natural menstrual cycle (35–55 days after the last egg retrieval), while 557 cases started after waiting for two or more natural menstrual cycles (56–140 days after the last egg retrieval). The implantation rate (11.1% vs 13.7%), CPR (26.4% vs 30.4%) and live birth rate (21.4% vs 23.4%) in the discontinuous treatment group were higher than in the continuous treatment cycle group, however, differences were not significant, indicating that delaying for two or more natural menstrual cycles may not have any advantage over continuous cycles. In a large retrospective study, 4404 patients were assessed on whether delayed frozen ETs improved CPRs and live birth rates. It was found that when participants were subjected to the same COS protocol, differences in CPRs, live birth rates, or early abortion rates between the immediate and delayed FET groups were insignificant. Moreover, differences in mean gestational age, mean birth weight, low birth weight and very low birth weight between the immediate and delayed FET groups were insignificant.26 Clinically, the choice for using delayed treatment by doctors and patients may be due to concerns that the ovulation induction regimen may adversely impact the ovary, endometrium, or the endocrine system, which may negatively affect fertilisation and implantation. However, various studies suggest that these concerns may not be warranted25 27 and that one endometrial regeneration cycle should be sufficient for embryonic implantation.28
In this study, endometrial thickness and infertility type were identified to be independent factors affecting the CPR after IUI. It has been reported that endometrial thickness can be used as an indicator of endometrial receptivity. Studies have associated thin endometria with low pregnancy rates,29 probably due to inefficient implantations.30 A study of the relationship between endometrial thickness and pregnancy outcomes in 1065 IUI cycles found that abnormal (too high or too low) endometrial thickness negatively affects CPRs and that CPR was highest when peak endometrial thickness was between 10.5 and 13.9 mm.31 However, other studies did not find any correlations between the two, suggesting that endometrial thickness is not a good prognostic factor for IUI success.32 The correlation between infertility type and CPR is also controversial.33 The prognosis of secondary infertility is better than that of primary infertility because patients with primary infertility may have infertility factors that are not easily identifiable, such as sperm egg binding disorders and poor endometrial receptivity.
In this study, we retrospectively reviewed all IUI cases at the Reproductive Medicine Centre of Lianyungang Maternal and Child Health Hospital from 1 January 2017 to 31 December 2019. These data are stored in the medical records system and have a high reliability. However, this study has some limitations. First, to avoid confounders that may be introduced by repeated inclusions of multiple cycles involving the same couple, only data on the first two ovulation induction IUI treatment cycles were included for each couple. Thus, we could not determine if patients who underwent more than two ovulation induction IUI treatment cycles can benefit from delaying treatment at different stages of the treatment process. Second, since our study is retrospective in nature and covered a short time span, our conclusions are conservative. Our findings should be validated via multicentre studies involving larger sample sizes or prospective randomised controlled trials. Additionally, although only a few variables were included in this study, additional factors may cause bias. Therefore, future studies should include more variables.
Conclusions
Prolonging the time interval between two ovulation induction IUI treatment cycles does not significantly improve pregnancy outcomes. In the absence of clear clinical indications, it may not be necessary to deliberately prolong time intervals between treatments.
Supplementary Material
Footnotes
SZ and H-HT contributed equally.
Contributors: SZ and M-LZ contributed to the conception and design of the study. SZ and H-HT were responsible for data collection and checking. SZ and H-HT performed the data analysis, interpretation and manuscript drafting. M-LZ supervised the project administration. All authors read and approved the final manuscript. SZ is responsible for the overall content as guarantor.
Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the Lianyungang maternal and child health hospital youth talent fund training project (no.KY202106).
Competing interests: None declared.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review: Not commissioned; externally peer reviewed.
Data availability statement
Data are available on reasonable request.
Ethics statements
Patient consent for publication
Not applicable.
Ethics approval
This study was approved by the Ethics Committee (Institutional Review Board) of Lianyungang Maternal and Child Health Hospital (no. LYG-MEP2021013). Written informed consent was waived due to the retrospective nature, and patients’ data were used anonymously.
References
- 1.Veltman-Verhulst SM, Hughes E, Ayeleke RO. Intra-Uterine insemination for unexplained subfertility. Cochrane Database Syst Rev 20162020;3:CD001838. 10.1002/14651858.CD001838.pub5 [DOI] [PubMed] [Google Scholar]
- 2.Horowitz E, Mizrachi Y, Farhi J, et al. Modified natural-cycle cryopreserved embryo transfer: is a washout period needed after a failed fresh cycle? Reprod Biomed Online 2019;39:439–45. 10.1016/j.rbmo.2019.05.003 [DOI] [PubMed] [Google Scholar]
- 3.Lattes K, Checa MA, Vassena R, et al. There is no evidence that the time from egg retrieval to embryo transfer affects live birth rates in a freeze-all strategy. Hum Reprod 2017;32:368–74. 10.1093/humrep/dew306 [DOI] [PubMed] [Google Scholar]
- 4.Ozgur K, Bulut H, Berkkanoglu M, et al. Frozen embryo transfer can be performed in the cycle immediately following the freeze-all cycle. J Assist Reprod Genet 2018;35:135–42. 10.1007/s10815-017-1048-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Reichman DE, Chung P, Meyer L, et al. Consecutive gonadotropin-releasing hormone-antagonist in vitro fertilization cycles: does the elapsed time interval between successive treatments affect outcomes? Fertil Steril 2013;99:1277–82. 10.1016/j.fertnstert.2012.11.044 [DOI] [PubMed] [Google Scholar]
- 6.Kaye L, Marsidi A, Rai P, et al. Frozen blastocyst transfer outcomes in immediate versus delayed subsequent cycles following GnRH agonist or hCG triggers. J Assist Reprod Genet 2018;35:669–75. 10.1007/s10815-017-1111-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Volodarsky-Perel A, Eldar-Geva T, Holzer HEG, et al. Cryopreserved embryo transfer: adjacent or non-adjacent to failed fresh long GnRH-agonist protocol IVF cycle. Reprod Biomed Online 2017;34:267–73. 10.1016/j.rbmo.2016.11.013 [DOI] [PubMed] [Google Scholar]
- 8.Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004;81:19–25. 10.1016/j.fertnstert.2003.10.004 [DOI] [PubMed] [Google Scholar]
- 9.World Health Organization . Laboratory manual for the examination and processing of human semen. 5th edn. Geneva: WHO, 2010. [Google Scholar]
- 10.Guttmacher AF. The role of artificial insemination in the treatment of human sterility. Bull N Y Acad Med 1943;19:573–91. [PMC free article] [PubMed] [Google Scholar]
- 11.Kohlberg K. Arzt und Samenübertragung. Dtsch med Wochenschr 1953;78:855–6. 10.1055/s-0028-1131381 [DOI] [PubMed] [Google Scholar]
- 12.Kohlberg K. Die praxis Der Samenübertragung beim Menschen. Dtsch med Wochenschr 1953;78:835–9. 10.1055/s-0028-1131375 [DOI] [PubMed] [Google Scholar]
- 13.Cohlen B, Bijkerk A, Van der Poel S, et al. IUI: review and systematic assessment of the evidence that supports global recommendations. Hum Reprod Update 2018;24:300–19. 10.1093/humupd/dmx041 [DOI] [PubMed] [Google Scholar]
- 14.Duran HE, Morshedi M, Kruger T, et al. Intrauterine insemination: a systematic review on determinants of success. Hum Reprod Update 2002;8:373–84. 10.1093/humupd/8.4.373 [DOI] [PubMed] [Google Scholar]
- 15.Lakatos E, Szigeti JF, Ujma PP, et al. Anxiety and depression among infertile women: a cross-sectional survey from Hungary. BMC Womens Health 2017;17:48. 10.1186/s12905-017-0410-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Rooney KL, Domar AD. The relationship between stress and infertility. Dialogues Clin Neurosci 2018;20:41–7. 10.31887/DCNS.2018.20.1/klrooney [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Massey AJ, Campbell BK, Raine-Fenning N, et al. Relationship between hair and salivary cortisol and pregnancy in women undergoing IVF. Psychoneuroendocrinology 2016;74:397–405. 10.1016/j.psyneuen.2016.08.027 [DOI] [PubMed] [Google Scholar]
- 18.Klonoff-Cohen H, Chu E, Natarajan L, et al. A prospective study of stress among women undergoing in vitro fertilization or gamete intrafallopian transfer. Fertil Steril 2001;76:675–87. 10.1016/S0015-0282(01)02008-8 [DOI] [PubMed] [Google Scholar]
- 19.An Y, Sun Z, Li L, et al. Relationship between psychological stress and reproductive outcome in women undergoing in vitro fertilization treatment: psychological and neurohormonal assessment. J Assist Reprod Genet 2013;30:35–41. 10.1007/s10815-012-9904-x [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Xu H, Ouyang N, Li R, et al. The effects of anxiety and depression on in vitro fertilisation outcomes of infertile Chinese women. Psychol Health Med 2017;22:37–43. 10.1080/13548506.2016.1218031 [DOI] [PubMed] [Google Scholar]
- 21.Palomba S, Daolio J, Romeo S, et al. Lifestyle and fertility: the influence of stress and quality of life on female fertility. Reprod Biol Endocrinol 2018;16:113. 10.1186/s12958-018-0434-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Horowitz E, Mizrachi Y, Farhi J, et al. Modified natural-cycle cryopreserved embryo transfer: is a washout period needed after a failed fresh cycle? Reprod Biomed Online 2019;39:439–45. 10.1016/j.rbmo.2019.05.003 [DOI] [PubMed] [Google Scholar]
- 23.Lattes K, Checa MA, Vassena R, et al. There is no evidence that the time from egg retrieval to embryo transfer affects live birth rates in a freeze-all strategy. Hum Reprod 2017;32:368–74. 10.1093/humrep/dew306 [DOI] [PubMed] [Google Scholar]
- 24.Ozgur K, Bulut H, Berkkanoglu M, et al. Frozen embryo transfer can be performed in the cycle immediately following the freeze-all cycle. J Assist Reprod Genet 2018;35:135–42. 10.1007/s10815-017-1048-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Reichman DE, Chung P, Meyer L, et al. Consecutive gonadotropin-releasing hormone-antagonist in vitro fertilization cycles: does the elapsed time interval between successive treatments affect outcomes? Fertil Steril 2013;99:1277–82. 10.1016/j.fertnstert.2012.11.044 [DOI] [PubMed] [Google Scholar]
- 26.He Y, Zheng H, Du H, et al. Delayed frozen embryo transfer failed to improve live birth rate and neonatal outcomes in patients requiring whole embryo freezing. Reprod Biol Endocrinol 2020;18:1. 10.1186/s12958-019-0560-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Santos-Ribeiro S, Siffain J, Polyzos NP, et al. To delay or not to delay a frozen embryo transfer after a failed fresh embryo transfer attempt? Fertil Steril 2016;105:1202–7. 10.1016/j.fertnstert.2015.12.140 [DOI] [PubMed] [Google Scholar]
- 28.Al-Serehi A, Mhoyan A, Brown M, et al. Placenta accreta: an association with fibroids and Asherman syndrome. J Ultrasound Med 2008;27:1623–8. 10.7863/jum.2008.27.11.1623 [DOI] [PubMed] [Google Scholar]
- 29.De Geyter C, Schmitter M, De Geyter M, et al. Prospective evaluation of the ultrasound appearance of the endometrium in a cohort of 1,186 infertile women. Fertil Steril 2000;73:106–13. 10.1016/S0015-0282(99)00484-7 [DOI] [PubMed] [Google Scholar]
- 30.Casper RF. It's time to pay attention to the endometrium. Fertil Steril 2011;96:519–21. 10.1016/j.fertnstert.2011.07.1096 [DOI] [PubMed] [Google Scholar]
- 31.Liu Y, Ye XY, Chan C. The association between endometrial thickness and pregnancy outcome in gonadotropin-stimulated intrauterine insemination cycles. Reprod Biol Endocrinol 2019;17:14. 10.1186/s12958-019-0455-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Weiss NS, van Vliet MN, Limpens J, et al. Endometrial thickness in women undergoing IUI with ovarian stimulation. How thick is too thin? A systematic review and meta-analysis. Hum Reprod 2017;32:1009–18. 10.1093/humrep/dex035 [DOI] [PubMed] [Google Scholar]
- 33.Dinelli L, Courbière B, Achard V, et al. Prognosis factors of pregnancy after intrauterine insemination with the husband's sperm: conclusions of an analysis of 2,019 cycles. Fertil Steril 2014;101:994–1000. 10.1016/j.fertnstert.2014.01.009 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data are available on reasonable request.