A reappraisal of ovarian stimulation strategies used in assisted reproductive technology.

Ovarian stimulation is a fundamental step in assisted reproductive technology (ART) with the intention of inducing ovarian follicle development prior to timed intercourse or intra-uterine insemination and facilitating the retrieval of multiple oocytes during a single in vitro fertilization (IVF) cycle. The basis of ovarian stimulation includes the administration of exogenous gonadotropins, with or without pre-treatment with oral hormonal therapy. Gonadotropin-releasing hormone agonist or antagonist is given in addition to the gonadotropins to prevent a premature rise of endogenous luteinizing hormone that would in turn lead to premature ovulation. With the advancement in technology, various stimulation protocols have been devised to cater for different patient needs. However, ovarian hyperstimulation syndrome and its serious complications may occur following ovarian stimulation. It is also evident that suboptimal ovarian stimulation strategies may have a negative impact on oogenesis, embryo quality, endometrial receptivity, and reproductive outcomes over recent years. This review describes the various forms of pre-treatment for ovarian stimulation and stimulation protocols, and aims to provide clinicians with the latest available evidence.

Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis.

BACKGROUND: In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed. OBJECTIVE AND RATIONALE: This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis. SEARCH METHODS: A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET. OUTCOMES: Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause. WIDER IMPLICATIONS: This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties.

Assisted reproduction in hepatitis carrier couples.

Chronic Hepatitis B virus (HBV) infection is endemic worldwide, and the prevalence is especially high in the Asia-Pacific regions. Despite its high prevalence, the literature regarding the impact of HBV infection on subfertility and fertility treatment remains limited and conflicting. Latest studies do not suggest any detrimental effect of HBV infection on the outcome of IVF/ICSI treatment in women having chronic HBV infection. There is evidence that HBV exists in ovarian tissue including oocyte and follicular fluid, and therefore has the potential risk of transmission to the embryo, which can explain the finding of vertical transmission despite immunoprophylaxis. Most recently, we have observed the evidence of HBV viral replication in female HBV carriers undergoing IVF/ICSI treatment. This raises the question of whether antiviral medication should be administered during ovarian stimulation in IVF/ICSI treatment cycles for women with chronic HBV infection to help reduce the chance of vertical transmission.

Presence of Hepatitis B virus DNA in follicular fluid in female Hepatitis B carriers and outcome of IVF/ICSI treatment: A prospective observational study.

OBJECTIVE: To determine the relationship between the presence of detectable HBV DNA in the follicular fluid in HBV carriers with IVF/ICSI treatment outcome. STUDY DESIGN: A prospective observational study conducted in the Assisted Reproductive Unit, a tertiary referral centre affiliated with the Department of Obstetrics and Gynecology, The Chinese University of Hong Kong; and the Union Reproductive Medicine Centre at Union Hospital, Hong Kong. The primary outcome measure was pregnancy rate. Secondary outcome measures were the prevalence of detectable HBV DNA in the follicular fluid, implantation rate, clinical pregnancy rate, ongoing pregnancy rate and live birth rate. RESULTS: HBV DNA was detected in the follicular fluid of 28 (43.8%) of the 64 women, and the mean level in this group in log10 copies/mL (±SD) was 4.36 ± 1.85. Women with detectable follicular fluid HBV DNA were younger, lighter, had longer duration of infertility, higher incidence of detectable serum HBV DNA (OR 4.592, 95% C I 2.333-9.038), and significantly wider range in the number of total fertilized, viable embryos, and blastocyst rate, but no difference in cycle characteristics, stimulation and pregnancy outcomes, although the almost doubled ongoing pregnancy/live birth rate per cycle initiated (60.7% versus 38.9%) failed to reach statistical significance due to the small numbers. CONCLUSION: Our results suggested HBV infection did not appear to be detrimental to the outcome of IVF/ICSI treatment.

Hepatitis B virus infection status and infertility causes in couples seeking fertility treatment-Indicator of impaired immune response?

PROBLEM: The relationship between hepatitis B (HBV) infection in infertile couples seeking in vitro fertilization (IVF) treatment and infertility causes is unknown. METHODS OF STUDY: A total of 831 infertile couples attending our unit seeking IVF during January to December 2015 were recruited. RESULTS: HBV infection was found in 6.3% and 7.3% of female and male partners, respectively, and infection in one or both partners was associated with less primary infertility (44.2% vs 55.1%, P=.038). Infected female partners had increased tubal (69.2% vs 43.2%, P<.001) and uterine (13.7% vs 3.1%, P<.001) causes and reduced idiopathic infertility, while infected male partners were associated with increased tubal (62.3% vs 43.4%, P=.004) causes and reduced endometriosis (62.3% vs 73.9%, P=.050). CONCLUSION: Our results suggest HBV infection in either partner was associated with tubal infertility. HBV infection in either partner probably increases the risk of pelvic infection in female partner through impaired immune response to sexually transmitted infections, with consequent tubal damage and infertility.