In Vitro Fertilization Treatment Cycles Research Articles

Investigating the effect of lifestyle risk factors upon number of aspirated and mature oocytes in in vitro fertilization cycles: Interaction with antral follicle count.

IntroductionThere is evidence demonstrating that certain lifestyle factors have a detrimental effect on fertility. Since such factors often coexist, possible synergistic effects merit further investigation. Thus we aimed to examine the cumulative impact of lifestyle factors on in vitro fertilization (IVF) early reproductive treatment outcomes and their interaction with measures of ovarian reserve.Materials and methodsBy following women who were starting their first fresh IVF cycle in 2 cohorts, the “Lifestyle study cohort” (hypothesis generating cohort, n = 242) and the “UppSTART study” (validation cohort, n = 432) in Sweden, we identified two significant risk factors acting independently, smoking and BMI, and then further assessed their cumulative effects.ResultsWomen with both these risk factors had an Incidence Rate Ratio (IRR) of 0.75 [(95% CI 0.61–0.94)] regarding the number of aspirated oocytes compared to women without these risk factors. Concerning the proportion of mature oocytes in relation to the total number of aspirated oocytes, the interaction between BMI and Antral Follicle Count (AFC) was significant (p-value 0.045): the lower the value of AFC, the more harmful the effect of BMI with the outcome.ConclusionsData shows that there is an individual as well as a cumulative effect of smoking and BMI on the number of aspirated and mature oocytes in fresh IVF treatment cycles. AFC might modify associations between BMI and the proportion of mature oocytes in relation to the total number of aspirated oocytes. These results highlight the importance of lifestyle factors on IVF early reproductive outcomes and provide additional evidence for the importance of preconception guidance for the optimization of IVF cycle outcome.

English

Women can still conceive naturally or through in vitro fertilization (IVF) with the one oviduct that is properly functioning if only one oviduct is blocked, however, the chances are decreased particularly if the blockage is close to the ovary (hydrosalpinx) because of wash out phenomena and toxic fluid produced by the fallopian tube that is blocked. In situations where only a single tube has hydrosalpinx specialists should advise patients appropriately and must be given options, to choose between undergoing salpingostomy, a surgical process that involves tubal reconstruction to expand their odds of getting pregnant naturally by removing the blockage or IVF treatment. For women with one working oviduct specialists must be on the lookout for ectopic pregnancy. This will enable early diagnosis of ectopic pregnancy and a treatment technique that spares the tube can be utilized. The patient is a woman of African origin with blood group O staying at Manyame Park Harare. She has never married before and has been trying to get pregnant from 2005. She eventually got a successful pregnancy in 2014 and delivered first child in 2015 after several interventions. Her infertility was initially due to the presence of hydrosalpinx on the left fallopian tube, scarring in the fimbriae of left tube, high prolactin level and was subsequently due to loss of the only working tube after ectopic pregnancy. The patient got pregnant whilst she was on bromocriptine, unfortunately the pregnancy did not last to full term. Chlomiphene was later added to her drug regiment and after six cycles she had an ectopic pregnancy which destroyed her only working tube. The patient then tried IVF treatments to achieve pregnancy. She underwent two IVF treatment cycles which failed to achieve pregnancy. The patient finally underwent tubal reconstruction microsurgery which enabled her to have two successful natural pregnancies. Gynaecologists must be vigilant in diagnosis of infertility factors and should give enough appropriate information to female patients when making decisions concerning fertility interventions. Key words: Fertility, in vitro fertilization (IVF), salpingostomy, hydrosalpinx, prolactin, fimbriae. &nbsp

The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study.

The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study.

Laparoscopic surgery: Any role in patients with unexplained infertility and failed in vitro fertilization cycles?

Patients who undergo several in-vitro fertilization (IVF) treatment cycles and fail to conceive present a frustrating problem to the clinician. When 1 cycle of IVF treatment fails, should we offer the couples to choose additional cycle of IVF instead of evaluation of the potential peritoneal factor? In cases of otherwise unexplained infertility, the investigation cannot be considered to be complete until laparoscopy has been performed. The aim of the study is to investigate the fertility outcome of laparoscopic treatment in infertile women with repeated IVF failures.This is a retrospective case-control study conducted in a tertiary care, academic teaching hospital from January 2012 to December 2015. Patients recruited in this study were classified into 2 groups. Study group (n = 45) were offered laparoscopy for evaluation of infertility, control group (n = 45) elected to proceed to IVF without laparoscopy. Diagnostic laparoscopy and subsequent excision of suspected endometriotic lesions, lysis of adhesion and treatment of tubal pathology were performed when indicated.Forty-four (97.8%) patients in study had pelvic pathologies and the treatment was performed at the same time. Twenty-four patients in study group conceived including 16 patients conceived spontaneously and 14 patients conceived with additional IVF following laparoscopy management. There was a significant difference in the ongoing pregnancy rates between patients conceived through IVF in study group and control group (41.9% vs 19.6%, P < .05).Laparoscopy in women with normal hysterosalpingography but recurrent IVF failures can detect unrecognized pelvic pathologies. Laparoscopy evaluation prior to additional cycle of IVF seems to improve the subsequent pregnancy rate.

The effect of performing hysteroscopy prior to the first in vitro fertilization (IVF) cycle on live birth rate

In this retrospective cohort study, a total of 707 couples underwent in vitro fertilization (IVF) at Hacettepe University Hospital between 01 January 2010 and 01 November 2014 with their chronologically first cycle were evaluated. Patients who have diagnostic hysteroscopy prior to first IVF cycle served as a study group (n = 42) and patients without diagnostic hysteroscopy served as control group (n = 282). In study group in all patients, diagnostic hysteroscopy was performed at the follicular phase of previous menstrual cycle, namely immediately before ovarian stimulation (OS) cycle. Demographic features, clinical characteristics and treatment outcomes were compared between the groups. The logistic regression analysis was performed in order to assess independent predictors of live birth rates (LBRs). There was no statistically significant difference between the groups for demographic features and OS cycle characteristics. Implantation rate (22.2% vs. 21.5%, p=.840), clinical pregnancy rate (33.3% vs. 28.7%, p=.541), and LBRs (23.8% vs. 18.5%, p=.420) were comparable. In logistic regression analysis, performing hysteroscopy prior to first IVF cycles per se without correcting anatomic abnormalities was not an independent predictor of LBRs (OR: 0.72, 95% CI: 0.310–1.68, p=.45). In conclusion, performing diagnostic hysteroscopy prior to first IVF treatment cycle without correcting any anatomic abnormalities did not improve LBRs.

More to the story than sperm: pregnancy rates with in vitro fertilization in same-sex female couples

For same-sex female (SSF) couples, assisted reproductive technology (ART) is prevalent as a means to family building. These couples may face significant burdens in finding insurance coverage for ART, choosing a sperm donor, and taking on the second parent adoption process in many states. Previous reports have compared pregnancy success rates using intrauterine insemination (IUI) between the general infertility population and members of same-sex female couples and have shown up to 67% cumulative pregnancy rates over 12 cycles.1 Of all evolving assisted reproductive technology, in vitro fertilization (IVF) provides the best overall chance of pregnancy. Additionally, IVF lends the unique opportunity for both members of a SSF couple to have involvement in treatment as either oocyte source or recipient. In order to best treat same-sex female couples, a population-specific criteria for prognosis should be established for IVF. The success of SSF in IVF treatment compared to the general infertility population is not yet established. We sought to determine if there exists a difference in IVF pregnancy rates between members of SSF couples and the general heterosexual infertility population. Retrospective chart review at a private infertility center. All IVF treatment cycles performed on patients in SSF relationships from 2016 to 2018 were analyzed. Both fresh and frozen transfers were identified, and we divided the data set into 2 groups, for female patients in same-sex and heterosexual couples. A binomial test was used to analyze the data using SPSS 21.0 (SPSS Inc., Chicago, IL, USA). A total of 205 treatment cycles were identified: 51 transfer cycles (42 frozen and 9 fresh) for SSF and 154 treatment cycles for heterosexual population (115 frozen and 39 fresh). Baseline characteristics between the SSF group and control group were the same, with a mean age in the SSF couples of 35.9 years old compared to 37.5 in the heterosexual group (p > 0.05). We found that the clinical pregnancy rate in the SSF population was significantly lower than the heterosexual patient population (39.2% vs. 55.8%, p = .025). Our analysis shows that patients in same-sex female relationships do not show a higher pregnancy rate with ART than the general infertility population. Given that this population showed a higher pregnancy rate with IUI than the general infertility population, we had expected a higher pregnancy rate with IVF as well. This data can be utilized to establish clinical guidelines in managing patient expectations about the outcomes of their treatment. Treating physicians need to look at SSF couples trying for pregnancy with ART with a very open mind when it comes to exploring all possibilities for care and exercise caution to not assume better pregnancy outcomes with IVF among this population. ART has the power to redefine modern family-building; a realistic view of all reproductive options can empower same-sex female couples to make the best treatment choices possible.

Anti-müllerian hormone levels are associated with live birth rates in ART, but the predictive ability of anti-müllerian hormone is modest

ObjectivesThe aim was to evaluate the association between serum Anti-Müllerian Hormone (AMH) level and cumulative live birth rates (LBR) in patients undergoing their first in vitro fertilization (IVF) treatment cycle, and to compare serum AMH levels with Antral Follicle Count (AFC) and Ovarian Sensitivity Index (OSI) as predictors of live birth. Study designA prospective cohort study of 454 patients under the age of 40 and with a regular menstrual cycle of 21-35 days, undergoing their first IVF treatment cycles between September 2010 and June 2015. Participants were divided into three groups based on their AMH level, (AMH ≤10, AMH 10-<30 and AMH ≥30 pmol/l). Any difference in AMH-distribution between patients with or without live birth was analyzed using a Mann-Whitney-test, and live birth rates were compared between groups by a chi-squared test for linear trend. The ability of AMH, OSI and AFC as predictors of live birth was assessed by a receiver operating characteristics-analysis and the area under the curve (AUC) was calculated. ResultsPatients with live birth had a higher AMH, median (range) 26 [0-137] pmol/l, compared with patients without live birth, AMH 22 [0-154] pmol/l, p = 0.035. Mean live birth rate (SD) was 0.36 (0.48) in the total cohort, 0.26 (0.44) in AMH-group <10, 0.34 (0.48) in AMH-group 10-<30, and 0.41(0.49) in AMH-group ≥30. Thus live birth rates increased with 8% per AMH-group (95% CI: 0.02 −0.14, p = 0.015). The AUC for AFC was 0.56, for AMH 0.57 and for OSI 0.63, respectively. ConclusionAMH concentration in serum is associated with live birth rates after IVF. Our results suggest that both AMH, AFC and OSI have an equal but modest predictive ability in relation to live birth rate.

Association between induced abortion history and later in vitro fertilization outcomes.

To establish an effective and safe clinical fertility strategy by investigating the relationship between abortion history and pregnancy outcomes of in vitro fertilization (IVF) treatment. In the present retrospective cohort study, data from IVF treatment cycles performed at a reproductive center in China between October 1, 2014, and October 31, 2015, were assessed. Outcomes were compared between women with a history of induced abortion and those without. There were 1532 IVF treatment cycles included; 454 patients had a history of induced abortion and 1078 did not. The spontaneous abortion rate was significantly higher (30/170 [17.6%] vs 41/420 [9.8%]; P=0.002) and the endometrium was significantly thinner (8.8±1.8 vs 9.7±1.8cm; P=0.001) among patients with a history of induced abortion compared with those without. In a subgroup analysis of patients with a history of induced abortion, women who had undergone surgical abortions had a lower live delivery rate compared with medical abortions (29/76 [38%] vs 101/378 [27%]; P=0.039). Further, women who had a history of more than two surgical abortions had lower live delivery and clinical pregnancy rates (both P<0.05). A history of induced abortion was associated with worse IVF outcomes, especially a history of more than two surgical abortions.

Hysteroscopy as an investigation tool in recurrent implantation failure in vitro fertilization.

Objectives:To evaluate the use of hysteroscopy in the assessment of uterine pathologies in infertile women with repeated implantation failure (RIF) after in vitro fertilization (IVF) and determine whether removal of such pathologies increased pregnancy rates in women with RIF.Methods:This prospective study was conducted at King Fahd Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia, between January 2010 and December 2015. The inclusion criteria were women who underwent IVF treatment cycles and ended in more than 2 RIF, and women who underwent hysterosalpingography (HSG). Hysteroscopies were performed, findings were recorded, and the clinical pregnancy rates were compared and assessed in patients with and without uterine cavity abnormality. All hysteroscopic procedures were performed by a single consultant.Results:Hysteroscopies were performed on 266 women who had at least 2 RIF. The average duration of infertility was 7.2±3.1 years. In 162 patients (60.9%), a hysteroscopy did not find any abnormality of the uterine cavity. In 104 patients (39.1%) there were one or more abnormal hysteroscopic findings. Hysterosalpingography was able to detect only 54 abnormalities (51.9%). The pregnancy rate was significantly higher in patients who were treated by a hysteroscopy for a detected uterine abnormality (39.4%).Conclusion:A hysteroscopy was able to detect intrauterine pathologies which were missed by other investigative modalities. We believe patients with a history of RIF should undergo hysteroscopic examination before any further cycles are considered.

Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures, and pregnancy outcomes among couples undergoing in vitro fertilization

BackgroundUse of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. MethodsThis analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005–2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. ResultsDetection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend=0.06). ConclusionsUsing IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes.

Effect of Weight Loss on In Vitro Fertilization Treatment Outcome

Background: To assess the effect of weight loss in overweight and/or obese women on the in vitro fertilization (IVF) treatment outcome before IVF cycles by a systematic review and meta-analysis of clinical trials. Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies were conducted. Systematic literature searches were conducted, and all randomized trials that evaluated the impact of weight loss in IVF treatment cycles were included in the study. Study selection, quality estimation, and data extractions were performed independently and in duplicate. Results: A total of 924 patients were enrolled in seven studies; the effects of weight loss on the IVF treatment outcome before the IVF treatment cycle were assessed. The clinical pregnancy rate (risk ratio [RR]: 1.61, 95% confidence interval [CI]: 1.15–2.27), miscarriage rate (RR: 0.56, 95% CI: 0.34–0.93), and live birth rate (RR: 1.86, 95% CI: 1.41–2.45) had a statistically significant difference between the intervention and control group. No significant differences were observed in the number of oocytes retrieved (weighted mean difference [WMD]: 0.84, 95% CI: −0.12–1.79), gonadotropin consumption (WMD: 2.59, 95% CI: −6.61–1.42), or the duration of stimulation (WMD: −0.46, 95% CI: −1.64–0.71). Conclusions: Before IVF treatment, obese and overweight women should lose weight by physical activity and/or dietary management because weight loss can improve pregnancy rate, reduce miscarriage rate, and meliorate live birth rate. At the same time, further prospective RCTs are required to establish which methods of weight loss are most suited to this purpose, as well as determining whether cut points for body mass index need to be recommended before accessing IVF.

Day three versus day two embryo transfer following in vitro fertilization or intracytoplasmic sperm injection.

Embryo transfer (ET) was traditionally performed two days after oocyte retrieval; however, developments in culture media have allowed embryos to be maintained in culture for longer periods. Delaying transfer from day two to day three would allow for further development of the embryo and might have a positive effect on pregnancy outcomes.To determine if there is any difference in live birth and pregnancy rates when ET is performed on day three, compared with day two, in infertile couples undergoing treatment with in vitro fertilization (IVF), including intracytoplasmic sperm injection (ICSI).We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (17th December 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and Biological Abstracts Databases (1980 to 2003), the National Research Register (NRR), the Medical Research Council's Clinical Trials Register, the NHS Centre for Reviews and Dissemination, citation lists of relevant publications, review articles and included studies, as well as abstracts of appropriate scientific meetings.Randomized controlled trials that compared day three versus day two embryo transfer after oocyte retrieval during an IVF or ICSI treatment cycle in subfertile couples.Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. The primary outcome measures were live birth rate and ongoing pregnancy rate.Ten studies involving 2027 women were included, but only three studies reported live birth and four reported ongoing pregnancy rates. The pooled odds ratios (day three compared to day two) were 1.07, 95% CI 0.84 to 1.37 for live birth and 1.05, 95% CI 0.83 to 1.32 for ongoing pregnancy. From ten studies, the pooled odds ratio for clinical pregnancy was 1.26, 95% CI 1.06 to 1.51. Sub-group analysis revealed that this advantage occurred in those undergoing ICSI cycles. A higher miscarriage rate with day 3 ET in ICSI cycles works to negate the increased clinical pregnancy rate, in agreement with the finding of no significant difference between treatments in live birth rate.Although an increase in clinical pregnancy rate with day three embryo transfer was demonstrated, at present there is not sufficient good quality evidence to suggest an improvement in live birth when embryo transfer is delayed from day two to day three.

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F®) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur®) and urinary follicle-stimulating hormone (uFSH, Fostimon®)-for ovarian stimulation in women undergoing invitro fertilization (IVF) treatment in the Netherlands. A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting. The mean total treatment costs were estimated as €5664 for follitropin alfa (95%UI €5167-6151), €5990 for hp-HMG (95%UI €5498-6488) and €5760 for uFSH (95%UI €5256-6246). The probability of a live birth was estimated at 36.1% (95%UI 27.4-44.3%), 33.9% (95%UI 26.2-41.5%) and 34.1% (95%UI 25.9-41.8%) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5% that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses. The present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

Hysteroscopy in recurrent in-vitro fertilisation failure (TROPHY): a multicentre, randomised controlled trial

The success rate of in-vitro fertilisation (IVF) remains low and many women undergo multiple treatment cycles. A previous meta-analysis suggested hysteroscopy could improve outcomes in women who have had recurrent implantation failure; however, studies were of poor quality and a definitive randomised trial was needed. In the TROPHY trial we aimed to assess whether hysteroscopy improves the livebirth rate following IVF treatment in women with recurrent failure of implantation. We did a multicentre, randomised controlled trial in eight hospitals in the UK, Belgium, Italy, and the Czech Republic. We recruited women younger than 38 years who had normal ultrasound of the uterine cavity and history of two to four unsuccessful IVF cycles. We used an independent web-based trial management system to randomly assign (1:1) women to receive outpatient hysteroscopy (hysteroscopy group) or no hysteroscopy (control group) in the month before starting a treatment cycle of IVF (with or without intracytoplasmic sperm injection). A computer-based algorithm minimised for key prognostic variables: age, body-mass index, basal follicle-stimulating hormone concentration, and the number of previous failed IVF cycles. The order of group assignment was masked to the researchers at the time of recruitment and randomisation. Embryologists involved in the embryo transfer were masked to group allocation, but physicians doing the procedure knew of group assignment and had hysteroscopy findings accessible. Participants were not masked to their group assignment. The primary outcome was the livebirth rate (proportion of women who had a live baby beyond 24 weeks of gestation) in the intention-to-treat population. The trial was registered with the ISRCTN Registry, ISRCTN35859078. Between Jan 1, 2010, and Dec 31, 2013, we randomly assigned 350 women to the hysteroscopy group and 352 women to the control group. 102 (29%) of women in the hysteroscopy group had a livebirth after IVF compared with 102 (29%) women in the control group (risk ratio 1·0, 95% CI 0·79-1·25; p=0·96). No hysteroscopy-related adverse events were reported. Outpatient hysteroscopy before IVF in women with a normal ultrasound of the uterine cavity and a history of unsuccessful IVF treatment cycles does not improve the livebirth rate. Further research into the effectiveness of surgical correction of specific uterine cavity abnormalities before IVF is warranted. European Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.

Hysteroscopy before in-vitro fertilisation (inSIGHT): a multicentre, randomised controlled trial

Hysteroscopy is often done in infertile women starting in-vitro fertilisation (IVF) to improve their chance of having a baby. However, no data are available from randomised controlled trials to support this practice. We aimed to assess whether routine hysteroscopy before the first IVF treatment cycle increases the rate of livebirths. We did a pragmatic, multicentre, randomised controlled trial in seven university hospitals and 15 large general hospitals in the Netherlands. Women with a normal transvaginal ultrasound of the uterine cavity and no previous hysteroscopy who were scheduled for their first IVF treatment were randomly assigned (1:1) to either hysteroscopy with treatment of detected intracavitary abnormalities before starting IVF (hysteroscopy group) or immediate start of the IVF treatment (immediate IVF group). Randomisation was done with web-based concealed allocation and was stratified by centre with variable block sizes. Participants, doctors, and outcome assessors were not masked to the assigned group. The primary outcome was ongoing pregnancy (detection of a fetal heartbeat at >12 weeks of gestation) within 18 months of randomisation and resulting in livebirth. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01242852. Between May 25, 2011, and Aug 27, 2013, we randomly assigned 750 women to receive either hysteroscopy (n=373) or immediate IVF (n=377). 209 (57%) of 369 women eligible for assessment in the hysteroscopy group and 200 (54%) of 373 in the immediate IVF group had a livebirth from a pregnancy during the trial period (relative risk 1·06, 95% CI 0·93-1·20; p=0·41). One (<1%) woman in the hysteroscopy group developed endometritis after hysteroscopy. Routine hysteroscopy does not improve livebirth rates in infertile women with a normal transvaginal ultrasound of the uterine cavity scheduled for a first IVF treatment. Women with a normal transvaginal ultrasound should not be offered routine hysteroscopy. The Dutch Organisation for Health Research and Development (ZonMW).

Basal serum testosterone levels correlate with ovarian reserve and ovarian response in cycling women undergoing in vitro fertilization

This study aimed to investigate the association between basal serum testosterone levels and in vitro fertilization (IVF) parameters in cycling women. A retrospective cohort study was performed at a clinical IVF center, and 495 women with regular menstruation were enrolled. Serum testosterone levels were measured before the start of IVF treatment cycle. We found that basal serum testosterone levels were negatively associated with female age and FSH/LH ratios. In contrast, we found a positive correlation between serum testosterone levels and the number of oocytes and available embryos. However, there was no significant association between testosterone levels and pregnancy outcome. Our results suggest that basal serum testosterone levels were significantly related to certain classic indicators of ovarian reserve, such as age and FSH/LH ratios. Increased testosterone levels improved ovarian response in cycling women, but they fail to predict pregnancy and miscarriage rate.

Long-acting FSH versus daily FSH for women undergoing assisted reproduction.

Assisted reproduction techniques (ART), such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), can help subfertile couples to create a family. It is necessary to induce multiple follicles, which is achieved by follicle stimulating hormone (FSH) injections. Current treatment regimens prescribe daily injections of FSH (urinary FSH either with or without luteinizing hormone (LH) injections or recombinant FSH (rFSH)).Recombinant DNA technologies have produced a new recombinant molecule which is a long-acting FSH, named corifollitropin alfa (Elonva) or FSH-CTP. A single dose of long-acting FSH is able to keep the circulating FSH level above the threshold necessary to support multi-follicular growth for an entire week. The optimal dose of long-acting FSH is still being determined. A single injection of long-acting FSH can replace seven daily FSH injections during the first week of controlled ovarian stimulation (COS) and can make assisted reproduction more patient friendly. To compare the effectiveness of long-acting FSH versus daily FSH in terms of pregnancy and safety outcomes in women undergoing IVF or ICSI treatment cycles. We searched the following electronic databases, trial registers and websites from inception to June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialized Register, MEDLINE, EMBASE, PsycINFO, CINAHL, electronic trial registers for ongoing and registered trials, citation indexes, conference abstracts in the ISI Web of Knowledge, LILACS, Clinical Study Results (for clinical trial results of marketed pharmaceuticals), PubMed and OpenSIGLE. We also carried out handsearches. We included all randomised controlled trials (RCTs) comparing long-acting FSH versus daily FSH in women who were part of a couple with subfertility and undertaking IVF or ICSI treatment cycles with a GnRH antagonist or agonist protocol. Two review authors independently performed study selection, data extraction and assessment of risk of bias. We contacted trial authors in cases of missing data. We calculated risk ratios for each outcome, and our primary outcomes were live birth rate and ovarian hyperstimulation syndrome (OHSS) rate. Our secondary outcomes were ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, any other adverse event (including ectopic pregnancy, congenital malformations, drug side effects and infection) and patient satisfaction with the treatment. Trials reported all outcomes, except patient satisfaction with the treatment. We included six RCTs with a total of 3753 participants and we graded the quality of the included studies as moderate. All studies included women with an indication for COS as part of an IVF/ICSI cycle with age ranging from 18 to 41 years. A comparison of long-acting FSH versus daily FSH did not show evidence of difference in effect on overall live birth rate (Risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.07; 2363 participants, eight studies; I² statistic = 44%) or OHSS (RR 1.00, 95% CI 0.74 to 1.37; 3753 participants, nine studies; I² statistic = 0%). We compared subgroups by dose of long-acting FSH. There was evidence of reduced live birth rate in women who received lower doses (60 to 120 μg) of long-acting FSH compared to daily FSH (RR 0.70, 95% CI 0.52 to 0.93; 645 participants, three studies; I² statistic = 0%). There was no evidence a difference between the groups in live births in the medium dose (150 to 180 μg) subgroup (RR 1.03, 95% CI 0.90 to 1.18; 1685 participants, four studies; I² statistic = 6%). There was no evidence of a difference between the groups in the clinical pregnancy rate (any dose), ongoing pregnancy rate (any dose), multiple pregnancy rate (any dose), miscarriage rate (low or medium dose), ectopic pregnancy rate (any dose), congenital malformation rate, congenital malformation rate; major or minor (low or medium dose). The use of a medium dose (150 to 180 μg) of long-acting FSH is a safe treatment option and equally effective compared to daily FSH in women with unexplained subfertility. There was evidence of reduced live birth rate in women receiving a low dose (60 to 120 μg) of long-acting FSH compared to daily FSH. Further research is needed to determine whether long-acting FSH is safe and effective for use in hyper- or poor responders and in women with all causes of subfertility.

Recombinant follicle-stimulating hormone and recombinant luteinizing hormone versus recombinant follicle-stimulating hormone alone during GnRH antagonist ovarian stimulation in patients aged ≥35 years: a randomized controlled trial.

Does luteinizing hormone (LH) supplementation improve live birth rate after in vitro fertilization (IVF) in patients aged ≥35 years receiving a gonadotrophin-releasing hormone (GnRH) antagonist protocol? There was no difference in live birth rate with use of LH during IVF in patients aged ≥35 years undergoing IVF treatment using a GnRH antagonist protocol. Use of GnRH analogues as part of a controlled ovarian hyperstimulation protocol during IVF treatment cycles decreases the amount of LH available to developing follicles. The role of LH supplementation for improving outcomes in patients undergoing controlled ovarian hyperstimulation as part of assisted reproduction treatments, particularly those involving a GnRH antagonist protocol, is unclear. It has been suggested that higher risk patients (e.g. age ≥35 years, poor ovarian reserve) may benefit from LH supplementation. This single-centre, randomized controlled trial was conducted from 1 October 2012 to 30 June 2014. A total of 240 women aged ≥35 years undergoing IVF received ovarian stimulation using a GnRH antagonist protocol, with recombinant follicle-stimulating hormone (r-FSH; Gonal-F(®)) starting from cycle day 2 or 3. GnRH antagonist (Cetrotide(®)) was administered on Day 5 of r-FSH administration. On Day 6, patients in the LH supplementation group were switched to r-FSH/r-LH (Pergoveris(®)) 150/75 IU/day. Randomization to study treatments was performed in blocks of 4 via a computer-generated random number list. Of the 240 patients randomized to treatment, 120 received r-FSH/r-LH and 120 received r-FSH. Patients were recruited from the IVFAS, An Sinh Hospital, Ho Chi Minh City, Vietnam. Live birth rate did not differ significantly (P > 0.05) between r-FSH/r-LH and r-FSH recipients (16.7 versus 17.5%; between-group difference 0.8, 95% confidence interval [CI] -9.5, 11.2). In addition, there were no significant differences between the r-FSH/r-LH and r-FSH groups with respect to the number of oocytes retrieved, implantation rate, miscarriage rate and clinical pregnancy rate. The open-label design could have introduced bias, and the relatively small sample size may have allowed detection of only the most common adverse events. In addition, the study was likely to be underpowered based on differences between the response rate assumptions used in the sample size calculation and the actual response rate during the study. The results of this study found no additional benefit from adding LH supplementation to ovarian stimulation with a GnRH antagonist protocol in women aged ≥35 years, and add to the body of evidence in this area. However, findings across studies are still inconsistent and additional research is needed before any clear recommendations for clinical practice can be made. This study was supported by the Research Center for Genetics and Reproductive Health, School of Medicine, Vietnam National University HCMC. The authors state that they have no financial or commercial conflicts of interest. The trial was registered with clinicaltrials.gov (NCT02244866).

The need to improve patient care through discriminate use of intracytoplasmic sperm injection (ICSI) and improved understanding of spermatozoa, oocyte and embryo biology

D. T. Carrell, A. Nyboe Andersen and D. J. Lamb Departments of Surgery (Urology), Obstetrics and Gynecology, and Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA, The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, and The Center for Reproductive Medicine, Scott Department of Urology and the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

Ovarian and adrenal androgens may be useful markers to predict oocyte competence and embryo development in older women

The aim of this retrospective analysis was to evaluate the association between serum levels of various hormones and in vitro fertilization (IVF) parameters in poor responder patients. Serum levels of anti-Müllerian hormone (AMH), dehydroepiandrosterone sulfate (DHEAS), androstenedione and testosterone were measured before the start of IVF treatment cycle. We found that serum AMH and DHEAS levels were positively correlated with the number of mature oocytes, fertilized oocytes and developed embryos, both in pregnant and in non-pregnant patients. In contrast, we found a positive correlation between serum androstenedione levels and IVF parameters in pregnant, but not in non-pregnant patients. In this latter group, androstenedione levels were positively associated with the number of mature oocytes and were negatively correlated with the number of fertilized oocytes. No correlation was observed with developed embryos. Finally, we reported a negative correlation between serum levels of testosterone and IVF parameters in pregnant women whereas no correlation was observed in non-pregnant patients. Our results suggest that serum AMH and DHEAS could be predictive for oocyte retrieval and embryo development. Moreover, the positive correlation between serum androstenedione levels and IVF parameters in pregnant patients, together with the lack of a consistent correlation in non-pregnant women seem to identify androstenedione as a more predictive marker for pregnancy outcome than testosterone. In addition, in our analysis testosterone shows a negative correlation with IVF parameters.