The risk of hypogonadism after testicular sperm extraction in men with various types of azoospermia: a prospective cohort study.

RESEARCH QUESTION: What is the risk of hypogonadism in men with obstructive azoospermia, non-obstructive azoospermia (NOA) or Klinefelter syndrome after testicular sperm extraction (TESE)? DESIGN: This prospective longitudinal cohort study was carried out between 2007 and 2015. RESULTS: Around 36% of men with Klinefelter syndrome, 4% of men with obstructive azoospermia and 3% of men with NOA needed testosterone replacement therapy (TRT). Klinefelter syndrome was strongly associated with TRT while no association was found between obstructive azoospermia or NOA and TRT. Irrespective of the pre-operative diagnosis, a higher testosterone concentration before TESE was associated with a lower chance of needing TRT. CONCLUSIONS: Men with obstructive azoospermia or NOA have a similar moderate risk of clinical hypogonadism after TESE, while this risk is much larger for men with Klinefelter syndrome. The risk of clinical hypogonadism is lower when testosterone concentrations are high before TESE.

Fertility preservation for women with breast cancer: a multicentre randomized controlled trial on various ovarian stimulation protocols.

STUDY QUESTION: Does ovarian stimulation with the addition of tamoxifen or letrozole affect the number of cumulus-oocyte complexes (COCs) retrieved compared to standard ovarian stimulation in women with breast cancer who undergo fertility preservation? SUMMARY ANSWER: Alternative ovarian stimulation protocols with tamoxifen or letrozole did not affect the number of COCs retrieved at follicle aspiration in women with breast cancer. WHAT IS KNOWN ALREADY: Alternative ovarian stimulation protocols have been introduced for women with breast cancer who opt for fertility preservation by means of banking of oocytes or embryos. How these ovarian stimulation protocols compare to standard ovarian stimulation in terms of COC yield is unknown. STUDY DESIGN, SIZE, DURATION: This multicentre, open-label randomized controlled superiority trial was carried out in 10 hospitals in the Netherlands and 1 hospital in Belgium between January 2014 and December 2018. We randomly assigned women with breast cancer, aged 18-43 years, who opted for banking of oocytes or embryos to one of three study arms; ovarian stimulation plus tamoxifen, ovarian stimulation plus letrozole or standard ovarian stimulation. Standard ovarian stimulation included GnRH antagonist, recombinant FSH and GnRH agonist trigger. Randomization was performed with a web-based system in a 1:1:1 ratio, stratified for oral contraception usage at start of ovarian stimulation, positive estrogen receptor (ER) status and positive lymph nodes. Patients and caregivers were not blinded to the assigned treatment. The primary outcome was number of COCs retrieved at follicle aspiration. PARTICIPANTS/MATERIALS, SETTING, METHODS: During the study period, 162 women were randomly assigned to one of three interventions. Fifty-four underwent ovarian stimulation plus tamoxifen, 53 ovarian stimulation plus letrozole and 55 standard ovarian stimulation. Analysis was according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: No differences among groups were observed in the mean (±SD) number of COCs retrieved: 12.5 (10.4) after ovarian stimulation plus tamoxifen, 14.2 (9.4) after ovarian stimulation plus letrozole and 13.6 (11.6) after standard ovarian stimulation (mean difference -1.13, 95% CI -5.70 to 3.43 for tamoxifen versus standard ovarian stimulation and 0.58, 95% CI -4.03 to 5.20 for letrozole versus standard ovarian stimulation). After adjusting for oral contraception usage at the start of ovarian stimulation, positive ER status and positive lymph nodes, the mean difference was -1.11 (95% CI -5.58 to 3.35) after ovarian stimulation plus tamoxifen versus standard ovarian stimulation and 0.30 (95% CI -4.19 to 4.78) after ovarian stimulation plus letrozole versus standard ovarian stimulation. There were also no differences in the number of oocytes or embryos banked. There was one serious adverse event after standard ovarian stimulation: one woman was admitted to the hospital because of ovarian hyperstimulation syndrome. LIMITATIONS, REASONS FOR CAUTION: The available literature on which we based our hypothesis, power analysis and sample size calculation was scarce and studies were of low quality. Our study did not have sufficient power to perform subgroup analysis on follicular, luteal or random start of ovarian stimulation. WIDER IMPLICATIONS OF THE FINDINGS: Our study showed that adding tamoxifen or letrozole to a standard ovarian stimulation protocol in women with breast cancer does not impact the effectiveness of fertility preservation and paves the way for high-quality long-term follow-up on breast cancer treatment outcomes and women's future pregnancy outcomes. Our study also highlights the need for high-quality studies for all women opting for fertility preservation, as alternative ovarian stimulation protocols have been introduced to clinical practice without proper evidence. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a grant (2011.WO23.C129) of 'Stichting Pink Ribbon', a breast cancer fundraising charity organization in the Netherlands. M.G., C.B.L. and R.S. declared that the Center for Reproductive Medicine, Amsterdam UMC (location VUMC) has received unconditional research and educational grants from Guerbet, Merck and Ferring, not related to the presented work. C.B.L. declared a speakers fee for Inmed and Yingming. S.C.L. reports grants and non-financial support from Agendia, grants, non-financial support and other from AstraZeneca, grants from Eurocept-pharmaceuticals, grants and non-financial support from Genentech/Roche and Novartis, grants from Pfizer, grants and non-financial support from Tesaro and Immunomedics, other from Cergentis, IBM, Bayer, and Daiichi-Sankyo, outside the submitted work; In addition, S.C.L. has a patent UN23A01/P-EP pending that is unrelated to the present work. J.M.J.S. reported payments and travel grants from Merck and Ferring. C.C.M.B. reports her role as unpaid president of the National guideline committee on Fertility Preservation in women with cancer. K.F. received unrestricted grants from Merck Serono, Good Life and Ferring not related to present work. K.F. declared paid lectures for Ferring. D.S. declared former employment from Merck Sharp & Dohme (MSD). K.F. declared paid lectures for Ferring. D.S. reports grants from MSD, Gedeon Richter and Ferring paid to his institution; consulting fee payments from MSD and Merck Serono paid to his institution; speaker honoraria from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono paid to his institution. D.S. has also received travel and meeting support from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono. No payments are related to present work. TRIAL REGISTRATION NUMBER: NTR4108. TRIAL REGISTRATION DATE: 6 August 2013. DATE OF FIRST PATIENT'S ENROLMENT: 30 January 2014.

Unmet support needs in donor sperm treatment: consequences for parents and their donor-children.

RESEARCH QUESTION: Are unmet needs for psychosocial counselling, peer support and friends/family support in parents directly and/or indirectly related to the mental health of parents and their donor-children? DESIGN: A cross-sectional sample of 214 parents participated in this quantitative study via an online questionnaire. The sample comprised mothers and fathers in a heterosexual relationship (n = 85), mothers in a lesbian relationship (n = 67) and single mothers (n = 62). Parents were recruited via three Dutch fertility clinics and four network organizations. Unmet support needs were measured with an adapted version of the Unmet Needs for Parenting Support questionnaire, changing the original items into items about donor conception. The items were derived from a qualitative study and checked by experts in donor conception. The parents' mental health was measured with the Adult Self Report and the donor-children's mental health with the Child Behaviour Checklist. A multigroup mediation analysis was conducted to explore relationships between parents' unmet support needs and their child's mental health, with the parents' mental health as a possible mediator. RESULTS: There were no direct relations between parents' unmet support needs and the mental health of donor-children. Unmet needs for psychosocial counselling, peer support and friends/family support for parents and children's mental health were indirectly related through the mental health of the parents: 0.074 (CI 95%  = 0.013-0.136; P = 0.017), 0.085 (CI 95% = 0.018-0.151; P = 0.036) and 0.063 (CI 95% = 0.019-0.106; P = 0.013), respectively. CONCLUSIONS: We recommend that fertility clinics, network organizations and authorities for infertility counsellors make their support available to parents for extended periods after their treatment. Further qualitative studies are necessary to assess how to relieve unmet support needs during donor sperm treatment.

Oocyte or ovarian tissue banking: decision-making in women aged 35 years or older facing age-related fertility decline.

RESEARCH QUESTION: Women who face age-related fertility decline have the option to safeguard future reproductive potential by banking oocytes or ovarian tissue. What are the methods that women prefer and what factors are important in their decision-making? DESIGN: Qualitative interview study, participants were recruited through monthly information sessions at a university hospital on oocyte banking, postings on social media, websites and newsletters and snowball sampling. Women had to be aged 35 years or older, single, childless and with a possible future desire for motherhood. Key concepts of the Health Belief Model were used as framework for the analyses. RESULTS: In total, 15 women participated in this qualitative study. For oocyte banking, they mentioned chances of success, extra time and faith in the technique and healthcare professionals as benefits. Risks for themselves or future children and costs were considered to be barriers in decision making. For ovarian tissue banking, the chances of success, the possibility of natural conception, the time investment and effect on menopausal symptoms were seen as benefits, and lack of experience and lack of information were considered barriers for themselves or their future children. Overall, they considered the procedures involved in oocyte banking as relatively 'easy', whereas ovarian tissue banking was seen as a more invasive procedure. CONCLUSION: Most women preferred oocyte banking over ovarian tissue banking because of its relative convenience. Future quantitative research in a larger cohort is necessary to confirm the findings and provide more insight into the relative importance of the different factors influencing women's decision.

Psychosocial counselling in donor sperm treatment: unmet needs and mental health among heterosexual, lesbian and single women.

RESEARCH QUESTION: What are the unmet needs after psychosocial counselling and mental health of women who opt for donor sperm treatment (DST), and are unmet counselling needs related to their mental health? DESIGN: This quantitative study included women in a heterosexual relationship (n = 19), women in a lesbian relationship (n = 25) and single women (n = 51) who opted for DST. Women were included if they had passed the DST intake procedure at a Dutch fertility clinic, were not pregnant and had no previous donor-child. Unmet needs were measured by a self-developed questionnaire based on specific topics identified in a previous qualitative study with added items from experts in the field of DST. The Adult Self Report was used to measure mental health. Relationships between unmet counselling needs and mental health were explored by multiple regression analyses. RESULTS: Fifty-two women (55%) reported unmet counselling needs. Women in heterosexual relationships mostly had unmet counselling needs on the topics of the decision to opt for DST (n = 11, 58%) and non-genetic parenthood (n = 11, 58%); women in lesbian relationships (n = 10, 40%) and single women (n = 14, 27%) mostly had unmet needs on the topic of choosing a sperm donor. In general, women had good mental health, but 13 (14%) met the criteria for clinical mental health problems. Women with more unmet counselling needs also had more mental health problems. CONCLUSIONS: Evidence-based guidelines for psychosocial counselling in DST should be developed. Only then can counselling be improved and be fit for purpose.

Guideline-based quality indicators for early pregnancy assessment units.

RESEARCH QUESTION: What valid guideline-based quality indicators can measure quality of care in early pregnancy assessment units (EPAU)? DESIGN: The systematic RAND-modified Delphi method was used to develop an indicator set from four evidence-based guidelines. An international expert panel was assembled to extract recommendations from these guidelines to establish quality indicators. RESULTS: A total of 119 recommendations were extracted. Eleven recommendations received a high median score and top five score above the 75th percentile and were selected as key recommendations. The expert panel reassessed 15 high score recommendations and top five score between the 50th and 75th percentile as well as one high score recommendation without consensus. Eight of these 16 recommendations were selected in the second round as key recommendations. The key recommendations were formulated into a set of 19 quality indicators, summarized as follows: women referred to an EPAU could be seen within 24 h and receive a clear explanation on treatment options; designated senior staff members could be responsible for the unit and staff could have had ultrasound training; protocols could be available for daily practice covering all treatment options for miscarriage and ectopic pregnancy; and an EPAU could have access to urine pregnancy testing and serum HCG assays. CONCLUSIONS: Nineteen quality indicators to measure early pregnancy care provided by EPAU were identified.

Gonadotrophins or clomiphene citrate in couples with unexplained infertility undergoing intrauterine insemination: a cost-effectiveness analysis.

RESEARCH QUESTION: What is the cost-effectiveness of gonadotrophins compared with clomiphene citrate in couples with unexplained subfertility undergoing intrauterine insemination (IUI) with ovarian stimulation under strict cancellation criteria? DESIGN: A cost-effectiveness analysis alongside a randomized controlled trial (RCT). Between July 2013 and March 2016, 738 couples were randomized to gonadotrophins (369) or clomiphene citrate (369) in a multicentre RCT in the Netherlands. The direct medical costs of both strategies were compared. Direct medical costs included costs of medication, cycle monitoring, insemination and, if applicable, pregnancy monitoring. Non-parametric bootstrap resampling was used to investigate the effect of uncertainty in estimates. The cost-effectiveness analysis was performed according to intention-to-treat. The incremental cost-effectiveness ratio (ICER) between gonadotrophins and clomiphene citrate for ongoing pregnancy and live birth was assessed. RESULTS: The mean costs per couple were €1534 for gonadotrophins and €1067 for clomiphene citrate (mean difference of €468; 95% confidence interval [CI] €464-472). As ongoing pregnancy rates were 31% in women allocated to gonadotrophins and 26% in women allocated to clomiphene citrate (relative risk 1.16, 95% CI 0.93-1.47), the ICER was €21,804 (95% CI €11,628-31,980) per additional ongoing pregnancy with gonadotrophins and €17,044 (95% CI €8998-25,090) per additional live birth with gonadotrophins. CONCLUSIONS: Gonadotrophins are more expensive compared with clomiphene citrate in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria, without being significantly more effective.

Gonadotrophins versus clomifene citrate with or without intrauterine insemination in women with normogonadotropic anovulation and clomifene failure (M-OVIN): a randomised, two-by-two factorial trial.

BACKGROUND: In many countries, clomifene citrate is the treatment of first choice in women with normogonadotropic anovulation (ie, absent or irregular ovulation). If these women ovulate but do not conceive after several cycles with clomifene citrate, medication is usually switched to gonadotrophins, with or without intrauterine insemination. We aimed to assess whether switching to gonadotrophins is more effective than continuing clomifene citrate, and whether intrauterine insemination is more effective than intercourse. METHODS: In this two-by-two factorial multicentre randomised clinical trial, we recruited women aged 18 years and older with normogonadotropic anovulation not pregnant after six ovulatory cycles of clomifene citrate (maximum of 150 mg daily for 5 days) from 48 Dutch hospitals. Women were randomly assigned using a central password-protected internet-based randomisation programme to receive six cycles with gonadotrophins plus intrauterine insemination, six cycles with gonadotrophins plus intercourse, six cycles with clomifene citrate plus intrauterine insemination, or six cycles with clomifene citrate plus intercourse. Clomifene citrate dosages varied from 50 to 150 mg daily orally and gonadotrophin starting dose was 50 or 75 IU daily subcutaneously. The primary outcome was conception leading to livebirth within 8 months after randomisation defined as any baby born alive after a gestational age beyond 24 weeks. Primary analysis was by intention to treat. We made two comparisons, one in which gonadotrophins were compared with clomifene citrate and one in which intrauterine insemination was compared with intercourse. This completed study is registered with the Netherlands Trial Register, number NTR1449. FINDINGS: Between Dec 8, 2008, and Dec 16, 2015, we randomly assigned 666 women to gonadotrophins and intrauterine insemination (n=166), gonadotrophins and intercourse (n=165), clomifene citrate and intrauterine insemination (n=163), or clomifene citrate and intercourse (n=172). Women allocated to gonadotrophins had more livebirths than those allocated to clomifene citrate (167 [52%] of 327 women vs 138 [41%] of 334 women, relative risk [RR] 1·24 [95% CI 1·05-1·46]; p=0·0124). Addition of intrauterine insemination did not increase livebirths compared with intercourse (161 [49%] vs 144 [43%], RR 1·14 [95% CI 0·97-1·35]; p=0·1152). Multiple pregnancy rates for the two comparisons were low and not different. There were three adverse events: one child with congenital abnormalities and one stillbirth in two women treated with clomifene citrate, and one immature delivery due to cervical insufficiency in a woman treated with gonadotrophins. INTERPRETATION: In women with normogonadotropic anovulation and clomifene citrate failure, a switch of treatment to gonadotrophins increased the chance of livebirth over treatment with clomifene citrate; there was no evidence that addition of intrauterine insemination does so. FUNDING: The Netherlands Organization for Health Research and Development.

Randomized Trial of a Lifestyle Program in Obese Infertile Women.

BACKGROUND: Small lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking. METHODS: We randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization. RESULTS: We assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in the analysis. The discontinuation rate in the intervention group was 21.8%. In intention-to-treat analyses, the mean weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group (P<0.001). The primary outcome occurred in 27.1% of the women in the intervention group and 35.2% of those in the control group (rate ratio in the intervention group, 0.77; 95% confidence interval, 0.60 to 0.99). CONCLUSIONS: In obese infertile women, a lifestyle intervention preceding infertility treatment, as compared with prompt infertility treatment, did not result in higher rates of a vaginal birth of a healthy singleton at term within 24 months after randomization. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1530.).

Gonadotrophins for ovulation induction in women with polycystic ovary syndrome.

BACKGROUND: Ovulation induction with follicle stimulating hormone (FSH) is a second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate. OBJECTIVES: To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS), and women who do not ovulate or conceive after clomiphene citrate. SEARCH METHODS: In January 2018, we searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, the World Health Organisation clinical trials register, Clinicaltrials.gov, LILACs, and PubMed databases, and Google Scholar. We checked references of in all obtained studies. We had no language restrictions. SELECTION CRITERIA: All randomised controlled trials reporting data on clinical outcomes in women with PCOS who did not ovulate or conceive on clomiphene citrate, and undergoing ovulation induction with urinary-derived gonadotrophins, including urofollitropin (uFSH) in purified FSH (FSH-P) or highly purified FSH (FSH-HP) form, human menopausal gonadotropin (HMG) and highly purified human menopausal gonadotrophin (HP-HMG), or recombinant FSH (rFSH), or continuing clomiphene citrate. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that described co-treatment with clomiphene citrate, metformin, luteinizing hormone, or letrozole. DATA COLLECTION AND ANALYSIS: Three review authors (NW, EK, and MvW) independently selected studies for inclusion, assessed risk of bias, and extracted study data. Primary outcomes were live birth rate per woman and multiple pregnancy per woman. Secondary outcomes were clinical pregnancy, miscarriage, incidence of ovarian hyperstimulation syndrome (OHSS) per woman, total gonadotrophin dose, and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the risk ratio (RR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria. MAIN RESULTS: The review included 15 trials with 2387 women. Ten trials compared rFSH with urinary-derived gonadotrophins (three compared rFSH with human menopausal gonadotrophin, and seven compared rFSH with FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P. One trial compared FSH with continued clomiphene citrate.Recombinant FSH (rFSH) versus urinary-derived gonadotrophinsThere may be little or no difference in the birth rate between rFSH and urinary-derived gonadotrophins (RR 1.21, 95% confidence interval (CI) 0.83 to 1.78; five trials, N = 505; I² = 9%; low-quality evidence). This suggests that for the observed average live birth per woman who used urinary-derived FSH of 16%, the chance of live birth with rFSH is between 13% and 28%. There may also be little or no difference between groups in incidence of multiple pregnancy (RR 0.86, 95% CI 0.46 to 1.61; eight trials, N = 1368; I² = 0%; low-quality evidence), clinical pregnancy rate (RR 1.05, 95% CI 0.88 to 1.27; eight trials, N = 1330; I² = 0; low-quality evidence), or miscarriage rate (RR 1.20, 95% CI 0.71 to 2.04; seven trials, N = 970; I² = 0; low-quality evidence). We are uncertain whether rFSH reduces the incidence of OHSS (RR 1.48, 95% CI 0.82 to 2.65, ten trials, n=1565, I² = 0%, very low-quality evidence).Human menopausal gonadotrophin (HMG) or HP-HMG versus uFSHWhen compared to uFSH, we are uncertain whether HMG or HP-HMG improves live birth rate (RR 1.28, 95% CI 0.65 to 2.52; three trials, N = 138; I² = 0%; very low quality evidence), or reduces multiple pregnancy rate (RR 2.13, 95% CI 0.51 to 8.91; four trials, N = 161; I² = 0%; very low quality evidence). We are also uncertain whether HMG or HP-HMG improves clinical pregnancy rate (RR 1.31, 95% CI 0.66 to 2.59; three trials, N = 102; I² = 0; very low quality evidence), reduces miscarriage rate (RR 0.33, 95% CI 0.06 to 1.97; two trials, N = 98; I² = 0%; very low quality evidence), or reduces the incidence of OHSS (RR 7.07, 95% CI 0.42 to 117.81; two trials, N = 53; very low quality evidence) when compared to uFSH.Gonadotrophins versus continued clomiphene citrateGonadotrophins resulted in more live births than continued clomiphene citrate (RR 1.24, 95% CI 1.05 to 1.46; one trial, N = 661; I² = 0%; moderate-quality evidence). This suggests that for a woman with a live birth rate of 41% with continued clomiphene citrate, the live birth rate with FSH was between 43% and 60%. There is probably little or no difference in the incidence of multiple pregnancy between treatments (RR 0.89, 95% CI 0.33 to 2.44; one trial, N = 661; I² = 0%; moderate-quality evidence). Gonadotrophins resulted in more clinical pregnancies than continued clomiphene citrate (RR 1.31, 95% CI 1.13 to 1.52; one trial, N = 661; I² = 0%; moderate-quality evidence), and more miscarriages (RR 2.23, 95% CI 1.11 to 4.47; one trial, N = 661; I² = 0%; moderate-quality evidence). None of the women developed OHSS. AUTHORS' CONCLUSIONS: There may be little or no difference in live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate between urinary-derived gonadotrophins and recombinant follicle stimulating hormone in women with polycystic ovary syndrome. For human menopausal gonadotropin or highly purified human menopausal gonadotrophin versus urinary follicle stimulating hormone we are uncertain whether one or the other improves or lowers live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate. We are uncertain whether any of the interventions reduce the incidence of ovarian hyperstimulation syndrome. We suggest weighing costs and convenience in the decision to use one or the other gonadotrophin. In women with clomiphene citrate failure, gonadotrophins resulted in more live births than continued clomiphene citrate without increasing multiple pregnancies.

Interventions for unexplained infertility: a systematic review and network meta-analysis.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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 (or combined with ICSI). DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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%. AUTHORS' CONCLUSIONS: 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.

Reproductive outcomes after oocyte banking for fertility preservation.

RESEARCH QUESTION: What are the reproductive outcomes of women who bank oocytes for fertility preservation? DESIGN: A prospective follow-up study of a cohort of 327 women who banked their oocytes for fertility preservation was carried out between July 2009 and August 2015. The indications for oocyte banking and outcomes of ovarian stimulation were collected from medical files. Follow-up data were obtained from an additional questionnaire. RESULTS: In total, 243 out of 327 women (74%) responded and 228 women (70%) consented to participate and returned the questionnaire. The median time to follow-up of these women was 31 months. A total of 101 women (44%) were trying, or had tried, to become pregnant after oocyte banking, of which 66 became pregnant (65%). Five women reported an unintended pregnancy. Of these, 71 women became pregnant, 76% conceived naturally, 7% through intracytoplasmic sperm injection with their vitrified-warmed oocytes and 17% by other medically assisted reproduction treatments. Six women attempted to achieve a pregnancy using their banked oocytes. Of the six pregnancies achieved in five women, two resulted in a live birth. A total of thirty-eight women reported a live birth at the time of follow-up. CONCLUSION: Oocyte banking can be considered a form of risk management or preventive medicine because it is not certain that the women will experience sterility in the future.

Intrauterine insemination versus intracervical insemination in donor sperm treatment.

BACKGROUND: The first-line treatment in donor sperm treatment consists of inseminations that can be done by intrauterine insemination (IUI) or by intracervical insemination (ICI). OBJECTIVES: To compare the effectiveness and safety of intrauterine insemination (IUI) and intracervical insemination (ICI) in women who start donor sperm treatment. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL in October 2016, checked references of relevant studies, and contacted study authors and experts in the field to identify additional studies. We searched PubMed, Google Scholar, the Grey literature, and five trials registers on 15 December 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs) reporting on IUI versus ICI in natural cycles or with ovarian stimulation, and RCTs comparing different cointerventions in IUI and ICI. We included cross-over studies if pre-cross-over data were available. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. We collected data on primary outcomes of live birth and multiple pregnancy rates, and on secondary outcomes of clinical pregnancy, miscarriage, and cancellation rates. MAIN RESULTS: We included six RCTs (708 women analysed) on ICI and IUI in donor sperm treatment. Two studies compared IUI and ICI in natural cycles, two studies compared IUI and ICI in gonadotrophin-stimulated cycles, and two studies compared timing of IUI and ICI. There was very low-quality evidence; the main limitations were risk of bias due to poor reporting of study methods, and serious imprecision.IUI versus ICI in natural cyclesThere was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in natural cycles (odds ratio (OR) 3.24, 95% confidence interval (CI) 0.12 to 87.13; 1 RCT, 26 women; very low-quality evidence). There was only one live birth in this study (in the IUI group). IUI resulted in higher clinical pregnancy rates (OR 6.18, 95% CI 1.91 to 20.03; 2 RCTs, 76 women; I² = 48%; very low-quality evidence).No multiple pregnancies or miscarriages occurred in this study.IUI versus ICI in gonadotrophin-stimulated cyclesThere was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in gonadotrophin-stimulated cycles (OR 2.55, 95% CI 0.72 to 8.96; 1 RCT, 43 women; very low-quality evidence). This suggested that if the chance of a live birth following ICI in gonadotrophin-stimulated cycles was assumed to be 30%, the chance following IUI in gonadotrophin-stimulated cycles would be between 24% and 80%. IUI may result in higher clinical pregnancy rates than ICI (OR 2.83, 95% CI 1.38 to 5.78; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). IUI may be associated with higher multiple pregnancy rates than ICI (OR 2.77, 95% CI 1.00 to 7.69; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). This suggested that if the risk of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was assumed to be 10%, the risk following IUI would be between 10% and 46%.We found insufficient evidence to determine whether there was any clear difference between the groups in miscarriage rates in gonadotrophin-stimulated cycles (OR 1.97, 95% CI 0.43 to 9.04; 2 RCTs, overall 67 pregnancies; I² = 50%; very low-quality evidence).Timing of IUI and ICIWe found no studies that reported on live birth rates.We found a higher clinical pregnancy rate when IUI was timed one day after a rise in blood levels of luteinising hormone (LH) compared to IUI two days after a rise in blood levels of LH (OR 2.00, 95% CI 1.14 to 3.53; 1 RCT, 351 women; low-quality evidence). We found insufficient evidence to determine whether there was any clear difference in clinical pregnancy rates between ICI timed after a rise in urinary levels of LH versus a rise in basal temperature plus cervical mucus scores (OR 1.31, 95% CI 0.42 to 4.11; 1 RCT, 56 women; very low-quality evidence).Neither of these studies reported multiple pregnancy or miscarriage rates as outcomes. AUTHORS' CONCLUSIONS: There was insufficient evidence to determine whether there was a clear difference in live birth rates between IUI and ICI in natural or gonadotrophin-stimulated cycles in women who started with donor sperm treatment. There was insufficient evidence available for the effect of timing of IUI or ICI on live birth rates. Very low-quality data suggested that in gonadotrophin-stimulated cycles, ICI may be associated with a higher clinical pregnancy rate than IUI, but also with a higher risk of multiple pregnancy rate. We concluded that the current evidence was too limited to choose between IUI or ICI, in natural cycles or with ovarian stimulation, in donor sperm treatment.

The FOAM study: is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial.

BACKGROUND: Tubal pathology is a causative factor in 20% of subfertile couples. Traditionally, tubal testing during fertility work-up is performed by hysterosalpingography (HSG). Hysterosalpingo-foam sonography (HyFoSy) is a new technique that is thought to have comparable accuracy as HSG, while it is less expensive and more patient friendly. HyFoSy would be an acceptable alternative for HSG, provided it has similar effectiveness in terms of patient outcomes. METHODS/DESIGN: We aim to compare the effectiveness and costs of management guided by HyFoSy or by HSG. Consenting women will undergo tubal testing by both HyFoSy and HSG in a randomized order during fertility work-up. The study group will consist of 1163 subfertile women between 18 and 41 years old who are scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male subfertility or a known contrast (iodine) allergy will be excluded. We anticipate that 7 % (N = 82) of the participants will have discordant test results for HyFoSy and HSG. These participants will be randomly allocated to either a management strategy based on HyFoSy or a management strategy based on HSG, resulting in either a diagnostic laparoscopy with chromopertubation or a strategy that assumes tubal patency (intrauterine insemination or expectant management). The primary outcome is ongoing pregnancy leading to live birth within 12 months after randomization. Secondary outcomes are patient pain scores, time to pregnancy, clinical pregnancy, miscarriage rate, multiple pregnancy rate, preterm birth rate and number of additional treatments. Costs will be estimated by counting resource use and calculating unit prices. DISCUSSION: This trial will compare the effectiveness and costs of HyFoSy versus HSG in assessing tubal patency in subfertile women. TRIAL REGISTRATION: Dutch Trial Register (NTR 4746, http://www.trialregister.nl ). Date of registration: 19 August 2014.

A revised prediction model for natural conception.

One of the aims in reproductive medicine is to differentiate between couples that have favourable chances of conceiving naturally and those that do not. Since the development of the prediction model of Hunault, characteristics of the subfertile population have changed. The objective of this analysis was to assess whether additional predictors can refine the Hunault model and extend its applicability. Consecutive subfertile couples with unexplained and mild male subfertility presenting in fertility clinics were asked to participate in a prospective cohort study. We constructed a multivariable prediction model with the predictors from the Hunault model and new potential predictors. The primary outcome, natural conception leading to an ongoing pregnancy, was observed in 1053 women of the 5184 included couples (20%). All predictors of the Hunault model were selected into the revised model plus an additional seven (woman's body mass index, cycle length, basal FSH levels, tubal status,history of previous pregnancies in the current relationship (ongoing pregnancies after natural conception, fertility treatment or miscarriages), semen volume, and semen morphology. Predictions from the revised model seem to concur better with observed pregnancy rates compared with the Hunault model; c-statistic of 0.71 (95% CI 0.69 to 0.73) compared with 0.59 (95% CI 0.57 to 0.61).

Recombinant luteinizing hormone (rLH) and recombinant follicle stimulating hormone (rFSH) for ovarian stimulation in IVF/ICSI cycles.

BACKGROUND: One of the various ovarian stimulation regimens used for in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles is the use of recombinant follicle-stimulating hormone (rFSH) in combination with a gonadotrophin-releasing hormone (GnRH) analogue. GnRH analogues prevent premature luteinizing hormone (LH) surges. Since they deprive the growing follicles of LH, the question arises as to whether supplementation with recombinant LH (rLH) would increase live birth rates. This is an updated Cochrane Review; the original version was published in 2007. OBJECTIVES: To compare the effectiveness and safety of recombinant luteinizing hormone (rLH) combined with recombinant follicle-stimulating hormone (rFSH) for ovarian stimulation compared to rFSH alone in women undergoing in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). SEARCH METHODS: For this update we searched the following databases in June 2016: the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and ongoing trials registers, and checked the references of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing rLH combined with rFSH versus rFSH alone in IVF/ISCI cycles. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data. We combined data to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I2 statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. Our primary outcomes were live birth rate and incidence of ovarian hyperstimulation syndrome (OHSS). Secondary outcomes included ongoing pregnancy rate, miscarriage rate and cancellation rates (for poor response or imminent OHSS). MAIN RESULTS: We included 36 RCTs (8125 women). The quality of the evidence ranged from very low to moderate. The main limitations were risk of bias (associated with poor reporting of methods) and imprecision.Live birth rates: There was insufficient evidence to determine whether there was a difference between rLH combined with rFSH versus rFSH alone in live birth rates (OR 1.32, 95% CI 0.85 to 2.06; n = 499; studies = 4; I2 = 63%, very low-quality evidence). The evidence suggests that if the live birth rate following treatment with rFSH alone is 17% it will be between 15% and 30% using rLH combined with rFSH.OHSS: There may be little or no difference between rLH combined with rFSH versus rFSH alone in OHSS rates (OR 0.38, 95% CI 0.14 to 1.01; n = 2178; studies = 6; I2 = 10%, low-quality evidence). The evidence suggests that if the rate of OHSS following treatment with rFSH alone is 1%, it will be between 0% and 1% using rLH combined with rFSH.Ongoing pregnancy rate: The use of rLH combined with rFSH probably improves ongoing pregnancy rates, compared to rFSH alone (OR 1.20, 95% CI 1.01 to 1.42; participants = 3129; studies = 19; I2 = 2%, moderate-quality evidence). The evidence suggests that if the ongoing pregnancy rate following treatment with rFSH alone is 21%, it will be between 21% and 27% using rLH combined with rFSH.Miscarriage rate: The use of rLH combined with rFSH probably makes little or no difference to miscarriage rates, compared to rFSH alone (OR 0.93, 95% CI 0.63 to 1.36; n = 1711; studies = 13; I2 = 0%, moderate-quality evidence). The evidence suggests that if the miscarriage rate following treatment with rFSH alone is 7%, the miscarriage rate following treatment with rLH combined with rFSH will be between 4% and 9%.Cancellation rates: There may be little or no difference between rLH combined with rFSH versus rFSH alone in rates of cancellation due to low response (OR 0.77, 95% CI 0.54 to 1.10; n = 2251; studies = 11; I2 = 16%, low quality evidence). The evidence suggests that if the risk of cancellation due to low response following treatment with rFSH alone is 7%, it will be between 4% and 7% using rLH combined with rFSH.We are uncertain whether use of rLH combined with rFSH improves rates of cancellation due to imminent OHSS compared to rFSH alone. Use of a fixed effect model suggested a benefit in the combination group (OR 0.60, 95% CI 0.40 to 0.89; n = 2976; studies = 8; I2 = 60%, very low quality evidence) but use of a random effects model did not support the conclusion that there was a difference between the groups (OR 0.82, 95% CI 0.34 to 1.97). AUTHORS' CONCLUSIONS: We found no clear evidence of a difference between rLH combined with rFSH and rFSH alone in rates of live birth or OHSS. The evidence for these comparisons was of very low-quality for live birth and low quality for OHSS. We found moderate quality evidence that the use of rLH combined with rFSH may lead to more ongoing pregnancies than rFSH alone. There was also moderate-quality evidence suggesting little or no difference between the groups in rates of miscarriage. There was no clear evidence of a difference between the groups in rates of cancellation due to low response or imminent OHSS, but the evidence for these outcomes was of low or very low quality.We conclude that the evidence is insufficient to encourage or discourage stimulation regimens that include rLH combined with rFSH in IVF/ICSI cycles.

Septum resection for women of reproductive age with a septate uterus.

BACKGROUND: Women with a septate uterus are at increased risk for subfertility, recurrent miscarriage, and preterm birth. Restoration of the anatomy of the uterus by hysteroscopic septum resection is an established intervention. This treatment has been assessed mainly in retrospective cohort studies, which suggested a positive effect on pregnancy outcomes. The major flaw in these studies is the before/after design, which will always favour the tested intervention. OBJECTIVES: To determine whether hysteroscopic septum resection in women of reproductive age with a septate uterus improves live birth rates and to assess the safety of this procedure. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register (inception to May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL CRSO) (inception to May 2016), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), PsycINFO (1806 to May 2016), and CINAHL database (1982 to May 2016). We also searched trial registers for ongoing and registered trials, reference lists, the Cochrane Library, unpublished dissertations and theses, conference abstracts, OpenGrey, LILACS, PubMed, and Google. SELECTION CRITERIA: We planned to include randomised controlled trials that assessed the effect on reproductive outcomes and the safety of hysteroscopic septum resection in women of reproductive age with a septate uterus. DATA COLLECTION AND ANALYSIS: If there had been studies to include, two review authors would have independently selected studies, assessed trial risk of bias, and extracted data. They would also have contacted study authors for additional information. MAIN RESULTS: As in the 2011 version of this review, we identified no randomised controlled trials for inclusion in this update. AUTHORS' CONCLUSIONS: Hysteroscopic septum resection in women of reproductive age with a septate uterus is performed worldwide to improve reproductive outcomes. At present, there is no evidence to support the surgical procedure in these women. Randomised controlled trials are urgently needed. Two trials are currently underway.

Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for subfertility associated with polycystic ovary syndrome.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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). AUTHORS' CONCLUSIONS: 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.

Reporting multiple cycles in trials on medically assisted reproduction.

Trials assessing effectiveness in medically assisted reproduction (MAR) should aim to study the desired effect over multiple cycles, as this reflects clinical practice and captures the relevant perspective for the couple. The aim of this study was to assess the extent to which multiple cycles are reported in MAR trials. A sample of randomized controlled trials (RCT) was collected on MAR, published in four time periods, in 11 pre-specified peer-reviewed journals; 253 trials were included: 196 on IVF, 37 on intrauterine insemination and 20 on ovulation induction. Forty-eight (19%) reported on multiple cycles, which was significantly more common in trials on intrauterine insemination and ovulation induction compared with trials on IVF (P < 0.01). Both trials on IVF were multi-centre trials, and those using live birth as primary outcome, reported significantly more often on multiple cycles (OR 3.7 CI 1.1 to 12.5) and (OR 8.7 CI 1.8 to 40.3), respectively. Trials designed to compare protocol variations reported multiple cycles less often (OR 0.07 CI 0.01 to 0.74). Most RCT on MAR, especially those on IVF, do not report cumulative pregnancy rates. As not all women become pregnant in their first cycle, the clinical significance of these trials is limited.

Perceptions of oocyte banking from women intending to circumvent age-related fertility decline.

INTRODUCTION: Women can now opt to bank their oocytes with the intention of increasing their chances of achieving a pregnancy after their fertility has declined. This exploratory study aimed to gain insight into how women, considering oocyte banking to circumvent age-related fertility decline, perceive this intervention. MATERIAL AND METHODS: We conducted a qualitative study in a Dutch university medical center and held in-depth interviews with women on the waiting list for oocyte banking. We recorded the interviews, transcribed them verbatim and used thematic analysis. RESULTS: All women were financially independent and lived in single-person urban households. They opted for oocyte banking because they wished to share parenthood with a future partner rather than becoming a single parent. This strong desire was key in their interpretation of all aspects of the intervention. Women set aside information about the limited success rates and potential risks, as they were optimistic about their own prognosis, thought that the chances for success were equally likely as the chances it would fail, and because of "anticipatory regret". They perceived oocyte banking as a "helping hand" to achieve shared parenthood. Although women found the costs of the intervention high, they were willing to invest their money to increase their chances for shared parenthood. CONCLUSIONS: Oocyte banking allows women to circumvent age-related fertility decline. The prospect of potential shared parenthood overrules the perceived health risks and burden. Health professionals should take this into account when informing potential users of oocyte banking.