Intra-uterine insemination for unexplained subfertility.

This review did not find sufficient evidence to support the use of one cycle regimen in preference to another in preparation for FET in subfertile women with regular ovulatory cycles. The most common modalities for FET are natural cycle with or without HCG trigger or endometrial preparation with HT, with or without GnRHa suppression. We identified only four direct comparisons of these two modalities and there was insufficient evidence to support the use of either one in preference to the other.

Clomiphene citrate (CC) is generally considered first-line treatment in women with anovulation due to polycystic ovary syndrome (PCOS). Ovulation induction with follicle-stimulating hormone (FSH; gonadotrophins) is second-line treatment for women who do not ovulate or conceive while taking CC. Metformin may increase the effectiveness of ovulation induction with gonadotrophins and may promote safety by preventing multiple pregnancy. To determine the effectiveness and safety of metformin co-treatment during ovulation induction with gonadotrophins with respect to rates of live birth and multiple pregnancy in women with PCOS. We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and the Cumulative Index to Nursing and Allied Health Literature (CINAH) on 8 June 2016, and the reference lists of included and other relevant studies. We searched ongoing trials registries in the World Health Organization (WHO) portal and on clinicaltrials.gov on 4 September 2016. We included randomised controlled trials (RCTs) reporting data on comparison of clinical outcomes in women with PCOS undergoing ovulation induction with gonadotrophins plus metformin versus gonadotrophins alone or gonadotrophins plus placebo. We used standard methodological procedures recommended by Cochrane. Primary review outcomes were live birth rate and multiple pregnancy rate. Secondary outcomes were ovulation rate, clinical pregnancy rate, ovarian hyperstimulation syndrome (OHSS) rate, miscarriage rate, cycle cancellation rate and adverse effects. We included five RCTs (with 264 women) comparing gonadotrophins plus metformin versus gonadotrophins. The gonadotrophin used was recombinant FSH in four studies and highly purified FSH in one study. Evidence was of low quality: The main limitations were serious risk of bias due to poor reporting of study methods and blinding of participants and outcome assessors. Live birth Metformin plus FSH was associated with a higher cumulative live birth rate when compared with FSH (odds ratio (OR) 2.31, 95% confidence interval (CI) 1.23 to 4.34; two RCTs, n = 180; I2 = 0%; low-quality evidence). This suggests that if the chance of live birth after FSH is assumed to be 27%, then the chance after addition of metformin would be between 32% and 60%. Other pregnancy outcomes Metformin use was associated with a higher ongoing pregnancy rate (OR 2.46, 95% CI 1.36 to 4.46; four RCTs, n = 232; I2 = 0%; low-quality evidence) and a higher clinical pregnancy rate (OR 2.51, 95% CI 1.46 to 4.31; five RCTs, n = 264; I2 = 0%; low-quality evidence). Multiple pregnancy Results showed no evidence of a difference in multiple pregnancy rates between metformin plus FSH and FSH (OR 0.55, 95% CI 0.15 to 1.95; four RCTs, n = 232; I2 = 0%; low-quality evidence) and no evidence of a difference in rates of miscarriage or OHSS. Other adverse effects Evidence was inadequate as the result of limited available data on adverse events after metformin compared with after no metformin (OR 1.78, 95% CI 0.39 to 8.09; two RCTs, n = 91; I2 = 0%; very low-quality evidence). Preliminary evidence suggests that metformin may increase the live birth rate among women undergoing ovulation induction with gonadotrophins. At this moment, evidence is insufficient to show an effect of metformin on multiple pregnancy rates and adverse events. Additional trials are necessary before we can provide further conclusions that may affect clinical practice.

Clinical management for unexplained infertility includes expectant management as well as active treatments, including ovarian stimulation (OS), intrauterine insemination (IUI), OS-IUI, and in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection (ICSI).Existing systematic reviews have conducted head-to-head comparisons of these interventions using pairwise meta-analyses. As this approach allows only the comparison of two interventions at a time and is contingent on the availability of appropriate primary evaluative studies, it is difficult to identify the best intervention in terms of effectiveness and safety. Network meta-analysis compares multiple treatments simultaneously by using both direct and indirect evidence and provides a hierarchy of these treatments, which can potentially better inform clinical decision-making. To evaluate the effectiveness and safety of different approaches to clinical management (expectant management, OS, IUI, OS-IUI, and IVF/ICSI) in couples with unexplained infertility. We performed a systematic review and network meta-analysis of relevant randomised controlled trials (RCTs). We searched electronic databases including the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, the Cochrane Central Register of Studies Online, MEDLINE, Embase, PsycINFO and CINAHL, up to 6 September 2018, as well as reference lists, to identify eligible studies. We also searched trial registers for ongoing trials. We included RCTs comparing at least two of the following clinical management options in couples with unexplained infertility: expectant management, OS, IUI, OS-IUI, and IVF (orcombined with ICSI). Two review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardised forms. The primary effectiveness outcome was a composite of cumulative live birth or ongoing pregnancy, and the primary safety outcome was multiple pregnancy. We performed a network meta-analysis within a random-effects multi-variate meta-analysis model. We presented treatment effects by using odds ratios (ORs) and 95% confidence intervals (CIs). For the network meta-analysis, we used Confidence in Network Meta-analysis (CINeMA) to evaluate the overall certainty of evidence. We included 27 RCTs (4349 couples) in this systematic review and 24 RCTs (3983 couples) in a subsequent network meta-analysis. Overall, the certainty of evidence was low to moderate: the main limitations were imprecision and/or heterogeneity.Ten RCTs including 2725 couples reported on live birth. Evidence of differences between OS, IUI, OS-IUI, or IVF/ICSI versus expectant management was insufficient (OR 1.01, 95% CI 0.51 to 1.98; low-certainty evidence; OR 1.21, 95% CI 0.61 to 2.43; low-certainty evidence; OR 1.61, 95% CI 0.88 to 2.94; low-certainty evidence; OR 1.88, 95 CI 0.81 to 4.38; low-certainty evidence). This suggests that if the chance of live birth following expectant management is assumed to be 17%, the chance following OS, IUI, OS-IUI, and IVF would be 9% to 28%, 11% to 33%, 15% to 37%, and 14% to 47%, respectively. When only including couples with poor prognosis of natural conception (3 trials, 725 couples) we found OS-IUI and IVF/ICSI increased live birth rate compared to expectant management (OR 4.48, 95% CI 2.00 to 10.1; moderate-certainty evidence; OR 4.99, 95 CI 2.07 to 12.04; moderate-certainty evidence), while there was insufficient evidence of a difference between IVF/ICSI and OS-IUI (OR 1.11, 95% CI 0.78 to 1.60; low-certainty evidence).Eleven RCTs including 2564 couples reported on multiple pregnancy. Compared to expectant management/IUI, OS (OR 3.07, 95% CI 1.00 to 9.41; low-certainty evidence) and OS-IUI (OR 3.34 95% CI 1.09 to 10.29; moderate-certainty evidence) increased the odds of multiple pregnancy, and there was insufficient evidence of a difference between IVF/ICSI and expectant management/IUI (OR 2.66, 95% CI 0.68 to 10.43; low-certainty evidence). These findings suggest that if the chance of multiple pregnancy following expectant management or IUI is assumed to be 0.6%, the chance following OS, OS-IUI, and IVF/ICSI would be 0.6% to 5.0%, 0.6% to 5.4%, and 0.4% to 5.5%, respectively.Trial results show insufficient evidence of a difference between IVF/ICSI and OS-IUI for moderate/severe ovarian hyperstimulation syndrome (OHSS) (OR 2.50, 95% CI 0.92 to 6.76; 5 studies; 985 women; moderate-certainty evidence). This suggests that if the chance of moderate/severe OHSS following OS-IUI is assumed to be 1.1%, the chance following IVF/ICSI would be between 1.0% and 7.2%. There is insufficient evidence of differences in live birth between expectant management and the other four interventions (OS, IUI, OS-IUI, and IVF/ICSI). Compared to expectant management/IUI, OS may increase the odds of multiple pregnancy, and OS-IUI probably increases the odds of multiple pregnancy. Evidence on differences between IVF/ICSI and expectant management for multiple pregnancy is insufficient, as is evidence of a difference for moderate or severe OHSS between IVF/ICSI and OS-IUI.

Acknowledgements: We would like to thank the following for their contributions to the 2020 update. All staff at the editorial base of the Cochrane Gynaecology and Fertility Review Group; and in particular, Helen Nagels (Managing Editor) and Information Specialist Marian Showell, for help with the literature searches. Drs Jeanette MacKenzie, Evi Vogiatzi and Rik van Eekelen who provided peer review comments. We also thank all the authors who replied to our email queries about their study: Dr Elisabet Clua, Dr Maria Luisa López‐Regalado and Dr OM Abuzeid. We also thank the following. Zabeena Pandian, who was the lead author of the original review and two subsequent updates. Other co‐authors for their contribution in the previous versions: Allan Templeton, Ozkan Ozturk, Gamal Serour, and Jane Marjoribanks. Statistician Andy Vail (University of Manchester University, UK) for methodological advice.

Laparoscopic ovarian drilling with and without medical ovulation induction may decrease the live birth rate in women with anovulatory PCOS and CC resistance compared with medical ovulation induction alone. But the sensitivity analysis restricted to only RCTs at low risk of selection bias suggests there is uncertainty whether there is a difference between the treatments, due to uncertainty around the estimate. Moderate-quality evidence shows that LOD probably reduces the number of multiple pregnancy. Low-quality evidence suggests that there may be little or no difference between the treatments for the likelihood of a clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. LOD may result in less OHSS. The quality of evidence is insufficient to justify a conclusion on live birth, clinical pregnancy or miscarriage rate for the analysis of unilateral LOD versus bilateral LOD. There were no data available on multiple pregnancy.

Fresh versus frozen embryo transfers in assisted reproduction.

Controlled ovarian hyperstimulation with intrauterine insemination (IUI) is a widely accepted treatment for unexplained and male subfertility. No consensus exists about the drug of first choice to be used as hyperstimulation. This randomized multicentre trial using a parallel design compares the efficacy of clomiphene citrate (CC) with that of recombinant FSH (rFSH). Couples with primary unexplained or male subfertility were randomized to receive CC or rFSH for ovarian hyperstimulation. The treatment was continued for up to four cycles unless pregnancy occurred. Cycles with more than three follicles were cancelled. Cumulative pregnancy rates and live birth rates were primary outcomes. Cancellation during treatment and multiple birth rates are secondary outcomes. Results were analysed following the intention-to-treat principle. Seventy couples with male subfertility and 68 couples with unexplained subfertility were included. Seventy-one women received CC, and 67 received rFSH. Twenty-seven pregnancies were observed in the CC group (38%) and 23 in the rFSH group (34.3%) relative risk (RR) 1.11 [95% confidence interval (95% CI) 0.71-1.73]. The live birth rate was 28.2% (20/71) and 26.9% (18/67) for CC and rFSH, respectively, RR 1.05 (95% CI 0.61-1.80). Overall, the live birth rates per cycle were 10% for CC-stimulated and 8.7% for rFSH stimulated cycles. The total multiple pregnancy rate was 6.0%. Thirty-five cycles (8.6%) were cancelled because of four or more follicles (CC, n = 17; rFSH, n = 18). In couples with primary unexplained or male subfertility participating in an IUI program, ovarian hyperstimulation can be achieved by CC or rFSH. No significant difference in live birth rates between CC and rFSH was observed. Being less expensive, CC seems the more cost-effective drug and therefore, can be offered as drug of first choice.

Background Embryo incubation and assessment is a vital step in assisted reproductive technology (ART). Traditionally, embryo assessment has been achieved by removing embryos from a conventional incubator daily for assessment of quality by an embryologist, under a light microscope. Over recent years time-lapse systems (TLSs) have been developed which can take digital images of embryos at frequent time intervals. This allows embryologists, with or without the assistance of computer algorithms, to assess the quality of the embryos without physically removing them from the incubator. The potential advantages of a TLS include the ability to maintain a stable culture environment, therefore limiting the exposure of embryos to changes in gas composition, temperature and movement. Additionally a TLS has the potential advantage of improving embryo selection for ART treatment by utilising additional information gained through monitoring embryo development. Objectives To determine the effect of a TLS compared to conventional embryo incubation and assessment on clinical outcomes in couples undergoing ART. Search methods A comprehensive search of all the major electronic databases, including grey literature, was undertaken in co-ordination with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group in July 2014 and repeated in November 2014 to confirm that the review is up to date. Selection criteria Two authors (SA and NA) independently scanned the titles and abstracts of the articles retrieved by the search. Full texts of potentially eligible randomised controlled trials (RCTs) were obtained and examined independently by the authors for their suitability according to the review inclusion criteria. In the case of doubt between the two authors, a third author (LC) was consulted to gain consensus. The selection process is documented with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart. Data collection and analysis Data were obtained and extracted by two authors. Disagreement was resolved by consensus. Trial authors were contacted by e-mail to obtain further study information and data. All extracted data were dichotomous outcomes and odds ratios (OR) were calculated on an intention-to-treat basis. Where enough data were available, meta-analysis was undertaken. Main results Three studies involving 994 women were found for inclusion. Data from all three studies were used to address comparison one, TLS with or without cell-tracking algorithms versus conventional incubation. No studies were found to address comparison two, TLS utilising cell-tracking algorithms versus TLS not utilising cell-tracking algorithms. There was only one study which reported live birth (n = 76). The results demonstrated no conclusive evidence of a difference in live birth rate per couple randomly assigned to the TLS and conventional incubation arms of the study (OR 1.1, 95% CI 0.45 to 2.73, 1 RCT, n = 76, moderate quality evidence). All three studies reported miscarriage (n = 994). There was no conclusive evidence of a difference in miscarriage rates per couple randomly assigned to the TLS and conventional incubation arms (OR 0.70, 95% CI 0.47 to 1.04, 3 RCTs, n = 994, I2 = 0%, low quality evidence). Only one study reported stillbirth rates (n = 76). There were equal numbers of stillbirths in both the TLS and conventional incubation arms of the study. Therefore, there was no evidence of a difference in the stillbirth rate per couple randomly assigned to TLS and conventional incubation (OR 1.0, 95% CI 0.13 to 7.49, 1 RCT, moderate quality evidence). All three studies reported clinical pregnancy rates (n = 994). There was no conclusive evidence of a difference in clinical pregnancy rate per couple randomly assigned to the TLS and conventional incubation arms (OR 1.23, 95% CI 0.96 to 1.59, 3 RCTs, n = 994, I2 = 0%, low quality evidence). None of the included studies reported cumulative clinical pregnancy rates. Authors' conclusions There is insufficient evidence of differences in live birth, miscarriage, stillbirth or clinical pregnancy to choose between TLS and conventional incubation. Further data explicitly comparing the incubation environment, the algorithm for embryo selection, or both, are required before recommendations for a change of routine practice can be justified.

Adhesions are fibrin bands that are a common consequence of gynaecological surgery. They are caused by conditions that include pelvic inflammatory disease and endometriosis. Adhesions are associated with comorbidities, including pelvic pain, subfertility, and small bowel obstruction. Adhesions also increase the likelihood of further surgery, causing distress and unnecessary expenses. Strategies to prevent adhesion formation include the use of fluid (also called hydroflotation) and gel agents, which aim to prevent healing tissues from touching one another, or drugs, aimed to change an aspect of the healing process, to make adhesions less likely to form.To evaluate the effectiveness and safety of fluid and pharmacological agents on rates of pain, live births, and adhesion prevention in women undergoing gynaecological surgery.We searched: the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and Epistemonikos to 22 August 2019. We also checked the reference lists of relevant papers and contacted experts in the field.Randomised controlled trials investigating the use of fluid (including gel) and pharmacological agents to prevent adhesions after gynaecological surgery.We used standard methodological procedures recommended by Cochrane. We assessed the overall quality of the evidence using GRADE methods. Outcomes of interest were pelvic pain; live birth rates; incidence of, mean, and changes in adhesion scores at second look-laparoscopy (SLL); clinical pregnancy, miscarriage, and ectopic pregnancy rates; quality of life at SLL; and adverse events.We included 32 trials (3492 women), and excluded 11. We were unable to include data from nine studies in the statistical analyses, but the findings of these studies were broadly in keeping with the findings of the meta-analyses. Hydroflotation agents versus no hydroflotation agents (10 RCTs) We are uncertain whether hydroflotation agents affected pelvic pain (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.52 to 2.09; one study, 226 women; very low-quality evidence). It is unclear whether hydroflotation agents affected live birth rates (OR 0.67, 95% CI 0.29 to 1.58; two studies, 208 women; low-quality evidence) compared with no treatment. Hydroflotation agents reduced the incidence of adhesions at SLL when compared with no treatment (OR 0.34, 95% CI 0.22 to 0.55, four studies, 566 women; high-quality evidence). The evidence suggests that in women with an 84% chance of having adhesions at SLL with no treatment, using hydroflotation agents would result in 54% to 75% having adhesions. Hydroflotation agents probably made little or no difference to mean adhesion score at SLL (standardised mean difference (SMD) -0.06, 95% CI -0.20 to 0.09; four studies, 722 women; moderate-quality evidence). It is unclear whether hydroflotation agents affected clinical pregnancy rate (OR 0.64, 95% CI 0.36 to 1.14; three studies, 310 women; moderate-quality evidence) compared with no treatment. This suggests that in women with a 26% chance of clinical pregnancy with no treatment, using hydroflotation agents would result in a clinical pregnancy rate of 11% to 28%. No studies reported any adverse events attributable to the intervention. Gel agents versus no treatment (12 RCTs) No studies in this comparison reported pelvic pain or live birth rate. Gel agents reduced the incidence of adhesions at SLL compared with no treatment (OR 0.26, 95% CI 0.12 to 0.57; five studies, 147 women; high-quality evidence). This suggests that in women with an 84% chance of having adhesions at SLL with no treatment, the use of gel agents would result in 39% to 75% having adhesions. It is unclear whether gel agents affected mean adhesion scores at SLL (SMD -0.50, 95% CI -1.09 to 0.09; four studies, 159 women; moderate-quality evidence), or clinical pregnancy rate (OR 0.20, 95% CI 0.02 to 2.02; one study, 30 women; low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention. Gel agents versus hydroflotation agents when used as an instillant (3 RCTs) No studies in this comparison reported pelvic pain, live birth rate or clinical pregnancy rate. Gel agents probably reduce the incidence of adhesions at SLL when compared with hydroflotation agents (OR 0.50, 95% CI 0.31 to 0.83; three studies, 538 women; moderate-quality evidence). This suggests that in women with a 46% chance of having adhesions at SLL with a hydroflotation agent, the use of gel agents would result in 21% to 41% having adhesions. We are uncertain whether gel agents improved mean adhesion scores at SLL when compared with hydroflotation agents (MD -0.79, 95% CI -0.82 to -0.76; one study, 77 women; very low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention. Steroids (any route) versus no steroids (4 RCTs) No studies in this comparison reported pelvic pain, incidence of adhesions at SLL or mean adhesion score at SLL. It is unclear whether steroids affected live birth rates compared with no steroids (OR 0.65, 95% CI 0.26 to 1.62; two studies, 223 women; low-quality evidence), or clinical pregnancy rates (OR 1.01, 95% CI 0.66 to 1.55; three studies, 410 women; low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention.Gels and hydroflotation agents appear to be effective adhesion prevention agents for use during gynaecological surgery, but we found no evidence indicating that they improve fertility outcomes or pelvic pain, and further research is required in this area. It is also worth noting that for some comparisons, wide confidence intervals crossing the line of no effect meant that clinical harm as a result of interventions could not be excluded. Future studies should measure outcomes in a uniform manner, using the modified American Fertility Society score. Statistical findings should be reported in full. No studies reported any adverse events attributable to intervention.

Ovarian response to stimulation during in-vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) plays an important role in determining live birth rates. Adjuvant treatments during ovarian stimulation that have different modes of action have been used to improve ovarian response to stimulation and outcome of IVF. Glucocorticoids (GCs) are a class of steroid hormones that have been used either alone or in combination with other stimulatory regimens in order to improve folliculogenesis and pregnancy rates. However, considerable uncertainty remains over whether administration of glucocorticoid during ovarian stimulation until oocyte recovery is superior to no glucocorticoid in improving live birth rates in women undergoing IVF/ICSI. To determine the safety and effectiveness of systemic glucocorticoids during ovarian stimulation for IVF and ICSI cycles. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Studies Online (CRSO), MEDLINE, Embase, CINAHL and PsycINFO from inception to 10 October 2016. We handsearched reference lists of articles, trial registers and relevant conference proceedings and contacted researchers in the field. We included randomised controlled trials (RCTs) comparing adjuvant treatment with systemic glucocorticoids during ovarian stimulation for IVF or ICSI cycles versus no adjuvant treatment. Two review authors independently selected studies, assessed risk of bias and extracted the data. Our primary outcome was live birth. Secondary outcomes included clinical pregnancy, multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS) and side-effects. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) and pooled the data using a fixed-effect model. The quality of the evidence was assessed using GRADE methods. Four RCTs were included in the review (416 women). The trials compared glucocorticoid supplementation during IVF stimulation versus placebo. Two of the studies had data in a form that we could not enter into analysis, so results include data from only two trials (310) women. For the outcome of live birth, data were available for only 212 women, as the larger study had data available from only one study centre.One of the studies gave inadequate description of randomisation methods, but the other was at low risk of bias in all domains. The evidence was rated as low or very low quality for all outcomes, mainly due to imprecision, with low sample sizes and few events.There was insufficient evidence to determine whether there was any difference between the groups in live birth rate (OR 1.08, 95% CI 0.45 to 2.58; 2 RCTs, n = 212, I2 = 0%, low-quality evidence). Our findings suggest that if the chance of live birth with placebo is assumed to be 15%, the chance following supplementation would be between 7% and 31%. There was no conclusive evidence of a difference in the clinical pregnancy rate (OR 1.69, 95% CI 0.98 to 2.90; 2 RCTs, n = 310, I2 = 0%, low-quality evidence).The evidence suggests that if the chance of clinical pregnancy with placebo is assumed to be 24%, the chance following treatment with glucocorticoid supplementation would be between 23% and 47%. There was also insufficient evidence to determine whether there was any difference between the groups in multiple-pregnancy rate (OR 3.32 , 95% CI 0.12 to 91.60; 1 RCT , n = 20, very low-quality evidence) or miscarriage rate (OR 1.00, 95% CI 0.05 to 18.57; 1 RCT, n = 20, very low-quality evidence). Neither of the studies reported OHSS or side-effects. The safety and effectiveness of glucocorticoid administration in women undergoing controlled ovarian hyperstimulation for IVF/ICSI cycles (until the day of oocyte retrieval) is unclear due to the small number of studies and low event rates. Whilst glucocorticoids possible increase the clinical pregnancy rate, there may be little or no impact on live birth rate. More research is needed.

ABSTRACTBackground:Infertility is a global health issue. The variation in the prevalence of unexplained infertility is attributed to the choice of investigation. There remains a knowledge gap on the impact of minimal and mild endometriosis on treatment outcomes following intrauterine insemination (IUI).Aim:The aim of this study was to compare treatment outcomes following ovarian stimulation (OS) and intrauterine insemination (IUI) between minimal and mild endometriosis versus unexplained infertility.Settings and Design:A retrospective analysis of women undergoing OS with intrauterine insemination during the year 20142020 in the Department of Reproductive Medicine and Surgery, Christian Medical College, Vellore, was considered for the study.Materials and Methods:Women with minimal and mild endometriosis or unexplained infertility diagnosed by diagnostic hysterolaparoscopy were included for the analysis. Univariate and multivariate analysis was done. The primary outcome was live birth rate (LBR) per cycle. The secondary outcomes measured were clinical pregnancy rate (CPR) , cumulative LBR (CLBR) per women, cumulative CPR (CCPR) per women and miscarriage rate.Statistical Analysis Used:The baseline parameters were compared using a t-test for continuous data, and categorical data were compared using the Chi-square/Fisher's exact test as appropriate. The outcomes were assessed using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CI).Results:There were no significant differences in CPR per cycle (14.28% vs. 18.8%, OR: 0.71; 95% CI: 0.401.28) and LBR per cycle (14.28% vs. 16.6%, OR: 0.84; 95% CI: 0.461.51) between the endometriosis and unexplained infertility groups. The cumulative LBR per woman and CCPR per woman also did not show any significant difference in between the two groups.Conclusion:The current study did not find any significant differences in cumulative LBR and CPR following OS-IUI in women with minimal or mild endometriosis and unexplained infertility.

Study question Is coital frequency (CF) influenced by intrauterine insemination with ovarian stimulation (IUI-OS) or expectant management in couples diagnosed with unexplained subfertility and a poor prognosis? Summary answer Couples allocated to expectant management had a higher CF than those allocated to IUI-OS. We found no evidence for associations with live birth. What is known already In couples with unexplained subfertility and a poor prognosis for natural conception, IUI-OS is generally first line treatment. Not much is known about the CF of these couples and to what extend they are still trying to conceive naturally and whether allocation to treatment or no treatment has an influence on CF. It is often postulated that the effect of IUI-OS might be derived from replacing coitus, especially in couples with longstanding subfertility i.e., over 24 months. Keeping a sex diary can provide insight on this. Study design, size, duration We performed a multicentre randomised-controlled-trial in couples with unexplained subfertility and a poor prognosis of conceiving naturally within one year. The couples were allocated in a 1:1 ratio to six months IUI-OS or six months expectant management. CF was assessed with diaries on moment of coitus in relation to the menstrual cycle. We intended to include 1091 couples but after almost 4 years, the study was stopped due to slow inclusion and lack of funding. Participants/materials, setting, methods We recruited 178 women; 86 women were assigned IUI-OS and 92 women expectant management. All participating Dutch-reading women were eligible for the online diaries (CASTOREDC). We defined the fertile window as 7 days before and 2 days after the estimated ovulation date for all cycles. We used the Mann Whitney U test for differences in CF and timing and logistic regression for the estimated association with live birth, adjusting for cycle number and treatment allocation. Main results and the role of chance After IUI-OS 28/86 women (33%) had a live birth and 12/92 (13%) after expectant management, yielding a relative risk of 2.5 (90%CI 1.49 to 4.17). Of the 178 recruited women 79 (44%) filled out at least one monthly diary on sex and/or menstruation dates, 35 after IUI-OS and 44 after EM. Of these10/35 (29%) had a live birth after IUI-OS and 3/44 (7%) after expectant management. In a total of 497 cycles, the 79 couples reported 2023 dates of coitus (average of 4.1 per cycle). The median CF was 3 (IQR: 0 to 7) in the IUI-OS group and 4 (1 to 6) in the expectant management group (p for difference: 0.08). The median CF that took place within the fertile window was 1 (0 to 3) in the IUI-OS group and 2 (0 to 3) in the expectant management group (p for difference: <0.01). No interaction was found between intercourse frequency or timing and treatment on live birth rate. The adjusted odds ratio for intercourse frequency was 0.93 (95%CI: 0.78-1.09). The adjusted odds ratio for intercourse timing was 0.94 (95%CI: 0.64-1.37). The odds ratio for allocated treatment was unaffected by these adjustments for intercourse frequency or timing. Limitations, reasons for caution Only 44% of trial population returned the CF and menstruation diaries which could have induced selection bias. We estimated the day of ovulation based on the date of the next menstrual period in the expectant management group of this pragmatic trial. Wider implications of the findings Even though the duration of subfertility was longstanding, couples in both groups still had coitus and the median CF was higher in the expectant management group. Trial registration number NTR5599

IVF is an accepted treatment for unexplained infertility. The objective of this review was to determine whether, for unexplained infertility, IVF improves the probability of live birth compared with: (i) expectant management; (ii) clomiphene citrate (CC); (iii) intrauterine insemination (IUI); (iv) IUI with controlled ovarian stimulation; and (v) gamete intra-Fallopian transfer (GIFT). This was based on a Cochrane review. Randomized controlled trials (RCTs) which compared the effectiveness of IVF with expectant management, CC, IUI with or without controlled ovarian stimulation and GIFT were included. Patients included couples with unexplained infertility. Live birth rate per woman/couple was the main outcome measure. Nine RCT were identified. Five RCTs were included in the final meta-analysis. There were no comparative data for CC and live birth rates for expectant management or GIFT. There was no significant difference in clinical pregnancy rates between IVF and expectant management. There was no evidence of a difference in live birth rates between IVF and IUI either without (OR 1.96, 95% CI 0.88 to 4.36) or with (OR 1.15, 95% CI 0.55 to 2.42) ovarian stimulation. Clinical pregnancy rates with IVF were significantly higher compared with GIFT (OR 2.14, 95% CI 1.08 to 4.22) as were the multiple pregnancy rates (OR 6.25, 95% CI 1.70 to 23.00). Clinical heterogeneity was present among the studies. There was no evidence of statistical heterogeneity. The effectiveness of IVF in unexplained infertility remains unproven. Larger trials with adequate power are warranted.

To report our experience on homologous intrauterine insemination (IUI) with gonadotropin controlled ovarian stimulation (COS) cycles and to examine different variables which could predict IUI success. This is a retrospective analysis of IUIs performed between January 1997 and December 2017. A total of 7359 COS IUI's procedures (2901 couples) were reviewed. Clinical pregnancy, live birth rate and age, body mass index (BMI), smoking habit, duration of infertility, sperm characteristics before and after treatment (total motile count, morphology, and vitality), day 3 FSH, total gonadotropin dose, and number of follicles were assessed by multivariate logistic regression analysis, and data were expressed as odds ratio (OR). The mean female age at the time of COS was 35.10 ± 3.93years. The most common single infertility diagnoses were unexplained infertility (53.55%), mild male factor (19.69%), and anovulation (10.95%). The total progressive motile sperm count (TPMC) was > 1 × 106/ml (mean 1.34 ± 1.08 × 106/ml). The clinical pregnancy rate was 9.38%, and the live birth rate was 7.19% per cycle. Twin pregnancies were 12.17%. Cumulative pregnancy was 21.89% and cumulative live birth rate was 17.58% per couple. Clinical pregnancy and live birth rates were significantly associated with female age [OR 0.97 (95% CI 0.95-0.99) and 0.95 (95% CI 0.93-0.97), respectively] and day 3 FSH [OR 0.91 (95% CI 0.87-0.94) e 0.90 (95% CI 0.87-0.94), respectively]. Clinical pregnancy rate and live birth rates after COS-IUIs were significantly influenced by female age and FSH levels. Clinical trial registration number: NCT03836118.

Tubal flushing for subfertility.