Live Birth Rate after Surgical and Expectant Management of Endometriomas after In Vitro Fertilization: A Systematic Review, Meta-Analysis, and Critical Appraisal of Current Guidelines and Previous Meta-Analyses

Abstract Study question To investigate the relationship between the number of oocytes and both the live birth rate after fresh embryo transfer and the cumulative live birth rate. Summary answer Above a 15-oocyte threshold, live birth rate (LBR) following fresh transfer plateaus, whereas a continuous increase in cumulative live birth rate (CLBR) is observed. What is known already Several lines of evidence indicate that number of oocytes represents a key point for in vitro fertilization (IVF) success. However, consensus is lacking regarding the optimal number of oocytes for expecting a live birth. This is a key question because it might impact the way practitioners initiate and adjust COS regimens. Study design, size, duration A systematic review and meta-analysis was performed. MEDLINE, EMBASE, and Cochrane Library were searched for studies published between January 01, 2004, and August 31, 2019 using the search terms: “(intracytoplasmic sperm injection or icsi or ivf or in vitro fertilization or fertility preservation)” and “(oocyte and number)” and “(live birth)”. Participants/materials, setting, methods Two independent reviewers carried out study selection, quality assessment using the adapted Newcastle-Ottawa Quality Assessment Scales, bias assessment using ROBIN-1 tools, and data extraction according to Cochrane methods. Independent analyses were performed according to the outcome (LBR and CLBR). The mean-weighted threshold of optimal oocyte number was estimated from documented thresholds, followed by a one-stage meta-analysis on articles with documented or estimable relative risks. Main results and the role of chance After reviewing 843 records, 64 full-text articles were assessed for eligibility. A total of 36 studies were available for quantitative syntheses. Twenty-one and 18 studies were included in the meta-analyses evaluating the relationship between the number of retrieved oocytes and LBR or CLBR, respectively. Given the limited number of investigations considering mature oocytes, association between the number of metaphase II oocytes and IVF outcomes could not be investigated. Concerning LBR, 7 (35.0%) studies reported a plateau effect, corresponding to a weighted mean of 14.4 oocytes. The pooled dose-response association between the number of oocytes and LBR showed a non-linear relationship, with a plateau beyond 15 oocytes. For CLBR, 4 (19.0%) studies showed a plateau effect, corresponding to a weighted mean of 19.3 oocytes. The meta-analysis of the relationship between the number of oocytes and CLBR found a non-linear relationship, with a continuous increase in CLBR, including for high oocyte yields. Limitations, reasons for caution Statistical models show a high degree of deviance, especially for high numbers of oocytes. Further investigations are needed to assess the generalization of those results to frozen mature oocytes, especially in a fertility preservation context, and to evaluate the impact of female age. Wider implications of the findings Above a 15-oocyte threshold, LBR following fresh transfer plateaus, suggesting that the freeze-all strategy should probably be performed. In contrast, the continuous increase in CLBR suggests that high numbers of oocytes could be offered to improve the chances of cumulative live births, after evaluating the benefit–risk balance. Trial registration number Not applicable

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Reproductive Outcomes of Women with Polycystic Ovarian Syndrome Following In-Vitro Fertilization — A Meta-Analysis and Systematic Review

Fertility & Reproduction ◽

10.1142/s2661318219500221 ◽

2019 ◽

Vol 01 (04) ◽

pp. 193-201

Author(s):

I-Ferne Tan ◽

Audrey J. R. Lim ◽

Inthrani R. Indran ◽

Michael S. Kramer ◽

Eu-Leong Yong

Keyword(s):

Live Birth ◽

Ovarian Hyperstimulation Syndrome ◽

Birth Rate ◽

Meta Analysis ◽

Live Birth Rate ◽

Ovarian Hyperstimulation ◽

Vitro Fertilization ◽

Ivf Outcomes ◽

Ovarian Syndrome

Background: Polycystic ovarian syndrome (PCOS) is a common cause of infertility in women. In-vitro fertilization (IVF) is required in 20–30% of women with PCOS trying to conceive. This is associated with increased risk of multiple gestation and ovarian hyperstimulation syndrome. Improvements in IVF techniques, safety standards, and the increased use of frozen embryos in recent years have lead to improved outcomes for women with PCOS. We performed a systematic review and meta-analysis to compare these outcomes with women without PCOS. Search Methods: A search of PubMed, EMBASE, the Cochrane Central Register of clinical trials, and Scopus databases for all articles published until November 16th, 2017 identified 21 studies comparing IVF outcomes in PCOS and non-PCOS women. Inclusion criteria were Rotterdam criteria PCOS, comparable IVF regimes, immediate IVF outcomes, and pregnancy outcomes. Studies were excluded if the control group included any PCOS criteria, donor oocytes, or in-vitro maturation. Outcomes: No difference was observed in live birth rate per cycle in women with vs. without PCOS (RR [Formula: see text] 1.01 [0.89, 1.16]; [Formula: see text] 82%), but the live birth rate per first cycle in PCOS cycles (RR [Formula: see text] 0.93 [0.88, 0.99]) was slightly lower. There was also no difference in the clinical pregnancy rate (RR 1.02 [0.89, 1.17]) or biochemical pregnancy rate (RR 1.03 [0.99, 1.08]) observed between the two groups. PCOS was associated with a significantly higher number of oocytes retrieved (mean difference [Formula: see text] 3.6; 95% CI [2.8, 4.4]), risk of miscarriage (RR 2.90 [2.09, 4.02]), and risk of ovarian hyperstimulation syndrome (RR 3.42 [2.28, 5.13]) per cycle. Conclusion: Despite a widespread perception of poor reproductive potential, women with PCOS experience IVF outcomes similar to those without PCOS. Although there is a slightly lower live birth rate during their first stimulation cycle, success rates are similar after multiple cycles. PCOS is associated with a higher risk of ovarian hyperstimulation syndrome. Further studies are required to mitigate this risk.

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P–545 Impact of screening for aneuploidies in blastocysts on single embryo transfer live birth rates. A systematic review and meta-analysis

Human Reproduction ◽

10.1093/humrep/deab130.544 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

L H Sordia-Hernandez ◽

F A Morale. Martinez ◽

A Flore. Rodriguez ◽

F Diaz-Gonzale. Colmenero ◽

P Leyv Camacho ◽

...

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Meta Analysis ◽

Genetic Diagnosis ◽

Live Birth Rate ◽

Single Embryo Transfer ◽

Reproductive Outcomes ◽

Vitro Fertilization

Abstract Study question Does the selection of blastocysts for single embryo transfer, through the diagnosis of aneuploidy, improves the live birth rate in patients undergoing in vitro fertilization? Summary answer There seems to be no statistical difference in live birth rates between embryos with preimplantational genetic diagnosis (PGD) and those without. What is known already: Initial reports indicate that reproductive results improve after the selection of embryos to be transfer after performing a biopsy of the blastomeres, or trophectoderm cells, with the subsequent comprehensive analysis of the chromosomes. However, these results are now questioned. Reports in the literature are contrasting, so the real utility of selecting all embryos through comprehensive chromosome analysis calls for a more careful analysis that compares the risks, costs, and benefits of these techniques and their actual utility in reproductive results of patients treated with in vitro fertilization. Specifically results related to live birth rate. Study design, size, duration A systematic review of prospective studies evaluating live birth rate after embryo transfer of embryos selected by blastocyst biopsy for aneuploidy analysis compared with reproductive outcomes in embryo transfers of embryos selected morphologically, without biopsy nor screening for aneuploidies. Participants/materials, setting, methods A literature search was performed in PubMed, EmBase, and the Cochrane library (from January 2000 to december 2019). A cumulative meta-analysis and evaluation of heterogeneity was performed for the clinical pregnancy rate. The quality of the included studies was assessed using Cochrane’s Risk of Bias tool and ROBINS I for observational studies Main results and the role of chance Seven studies were included, three were randomized controlled trials and four were non-randomized studies of intervention (NRSI). The included studies were published between 2013 and 2019. For the preimplantational genetic diagnosis, three studies used array comparative genomic hybridization, three studies used next generation sequencing and only one study used qPCR. A total of 1638 patients were included, only two studies excluded patients with advanced maternal age (>35 years), two studies studied patients with recurrent implantation failure and three studies patients with recurrent pregnancy loss. Regarding the assisted reproduction techniques (ART), only studies where embryos where biopsied after day five for the genetic diagnosis where considered, most used ICSI and performed frozen-thawed transfer of up to two embryos, only one study allowed patients to be transferred with more than two embryos per cycle. Reproductive outcomes (live birth rate, miscarriage rate, clinical pregnancy) were extracted considering the events per embryo transfer and calculating the pooled odds ratios (OR) with 95% confidence intervals (95%CI) as our main outcome, sensitivity analyses will be performed using the events per cycles to assess the robustness of the effect estimate. Preliminary meta-analyses resulted in a pooled OR of 1.45 (95%CI 0.24–8.78) for NRSI and 1.34 (95%CI 0.85–2.11) for RCT. Limitations, reasons for caution The main limitation was the quantity of studies with acceptable methodology. This generated heterogeneity, hindering the evaluation of the true impact of PGD in ART outcomes. The use of events per embryo transfer as a main outcome could bias the results favoring PGD as less embryos are usually transferred. Wider implications of the findings: Our results show that there are too few studies with adequate methodology to generate a conclusion about the true benefit of PGD. However, a slight tendency favoring the reproductive outcomes of PGD was found. Trial registration number PROSPERO CRD42020198866

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The Effect of Hysteroscopy on the Reproductive Outcomes of Infertile Women Without Intrauterine Pathologies: A Systematic Review and Meta-Analysis

10.20944/preprints202009.0649.v1 ◽

2020 ◽

Author(s):

Soo Yeon Yang ◽

Seon Heui Lee ◽

Seung-Joo Chon

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Cochrane Library ◽

Reproductive Outcomes ◽

Vitro Fertilization ◽

Infertile Women ◽

Ovid Medline ◽

Meta Analyses ◽

The Cochrane Library

(1) Background: The aim of this work was to systematically review existing studies on whether hysteroscopy improves the reproductive outcomes of women with infertility even in the absence of intrauterine pathologies when compared to women who did not receive a hysteroscopy. (2) Methods: We established the Participant-Intervention-Comparison-Outcome strategy and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to conduct a systematic review of 11 studies which were retrieved from 3 electronic databases: Ovid-Medline, Ovid-Embase, and the Cochrane Library. Two independent investigators extracted the data from the included studies and used the Cochrane risk-of-bias tool to assess their quality. (3) Results: The primary outcome measures were the clinical pregnancy rates (CPRs) and live birth rates (LBRs) in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Hysteroscopy in infertile women without intrauterine pathologies showed higher CPRs and LBRs than those in the same population who did not receive hysteroscopy in cases of recurrent implantation failure and IVF (odds ratio: 1.79 and 1.46, 95% confidence interval: 1.46-2.30 and 1.08-1.97 for CPR and LBR, respectively); however, the degree of significance was not as high for LBR. (4) Conclusions: Hysteroscopy before IVF/ICSI in infertile women without intrauterine pathologies may potentially be effective in improving the CPRs and LBRs in patients with RIF. Robust and high-quality randomized trials are warranted to confirm this finding.

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P–320 Endometrial flushing to improve fertility outcomes: a systematic review and meta-analysis

Human Reproduction ◽

10.1093/humrep/deab130.319 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

J Vaughan ◽

L Manna ◽

Y Cheong

Keyword(s):

Systematic Review ◽

Contrast Medium ◽

Live Birth ◽

Birth Rate ◽

Meta Analysis ◽

Implantation Rate ◽

Live Birth Rate ◽

Clinical Pregnancy ◽

Healthy Baby ◽

Meta Analyses

Abstract Study question Does flushing the endometrial cavity improve fertility outcomes in couples with infertility and what are the preferred flushing mediums? Summary answer Flushing the endometrial cavity appears to improve live birth rate, implantation rate and clinical pregnancy rate. There was no difference in miscarriage or complication rate. What is known already Live birth rate was improved in cleavage-stage transfer when the uterus was flushed with human chorionic gonadotropin (hCG) at a dose >500 IU in a Cochrane review (Craciunas L et al 2018). Chemical and clinical pregnancy rates and implantation rate may be improved by endometrial flushing with platelet-rich plasma (PRP) in a meta-analysis by Maleki-Hajiagha A et al 2020. Flushing the cavity with oil-based contrast at hysterosalpingography (HSG) improved pregnancy rates when compared with water-based contrast in a systematic review by Fang F et al 2018. Study design, size, duration Our study was a systematic review and meta-analysis. We searched MEDLINE (1946 to December 2020), Embase (1980 to December 2020), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1961 to 9 December 2020) PsychINFO (1806 to December 2020). We screened the titles of search results to identify studies for inclusion and then screened abstracts and full texts to ensure trials met search criteria. Participants/materials, setting, methods We included in this review all randomised controlled trials (RCTs), quasi-experimental or cohort studies evaluating intrauterine instillation or flushing with any medium, irrespective of timing of intervention and irrespective of language or country of origin. We performed the meta-analyses using a random-effects model and performed subgroup and sensitivity analysis. Two authors independently extracted the data. We calculated the risk ratio or odds ratio with 95% confidence intervals based on intention-to-treat or available data analysis. Main results and the role of chance We included 36 RCTs and 12 non-randomised trials including 12230 participants. The sample size varied from 15 to 1186. We included 11 comparisons. Primary outcomes were healthy baby rate and live birth rate. Healthy baby rate was not reported in any of the trials. Live birth rate favoured oil soluble contrast medium (at HSG) when compared to water based contrast medium (OR 0.64, 95% CI 0.52 to 0.78, 2 RCTs and 1 cohort study, 2050 participants, I2 = 86%) or no intervention (OR 3.53, 95% CI 1.64 to 7.60, 2 RCTs, 192 participants, I2 = 0%). With regards to our secondary outcomes: CSF instillation, HCG instillation, PRP instillation and oil-soluble contrast medium at HSG (over water-soluble contrast medium) were favoured for implantation rate and clinical pregnancy rate. There was no statistically significant difference in miscarriage or complication rate for any of the comparisons. All trials were at an overall high risk of bias when assessed on the following areas: sequence generation, allocation concealment, blinding of participants, personnel, and outcome assessors, incomplete outcome data, selective outcome reporting, and other sources of bias. Limitations, reasons for caution Only 36 studies included were RCTs. Twelve of the RCTs had post randomisation drop outs. There was a lack of detail on the instillation medium for several of the included studies. There was no placebo used in many of the control groups. All meta-analyses had high levels of heterogeneity. Wider implications of the findings: Our findings are in keeping with the literature suggesting a possible improvement in live birth rate following flushing the endometrium with oil soluble contrast medium when compared with a control group. Mechanistic studies are now required to understand how oil-based medium improves fertility. Trial registration number NA

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