Infertile women with a history of fertility-sparing surgery for borderline ovarian tumors: IVF outcomes and the association between IVF and tumor recurrence

The results of conservative (fertility-sparing) treatment in borderline ovarian tumors vary depending on age and histological type.

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

Study question Is the probability of pregnancy different in women with and without dyslipidaemia undergoing in vitro fertilization (IVF)? Summary answer Women with dyslipidaemia demonstrate lower probability of achieving pregnancy compared to those without dyslipidaemia when undergoing IVF. What is known already Dyslipidaemia, including high concentrations of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) or triglycerides (TG), as well as low levels of high-density lipoprotein cholesterol (HDL-C) may affect fertility. Although the exact pathogenetic mechanisms have not been fully elucidated, dyslipidaemia-induced endothelial dysfunction may be identified. However, its specific impact on IVF outcomes remains inadequately studied. Study design, size, duration This systematic review and meta-analysis included cohort studies which evaluated the impact of dyslipidaemia on IVF outcomes. A comprehensive literature search of PubMed, Scopus and Google Scholar was conducted until January 2024. The primary outcome was live birth rates, while secondary outcomes included clinical pregnancy, cumulative live birth and miscarriage rates. Participants/materials, setting, methods Data from identified studies were independently extracted by two reviewers, including demographic, methodological and clinical information. Study quality was assessed using the Newcastle-Ottawa Scale. Statistical heterogeneity was evaluated using the I² statistic, and meta-analyses were conducted using random- or fixed-effects models, depending on the presence of significant heterogeneity. Results were expressed as relative risks (RR) or weighted mean differences (WMD) with 95% confidence intervals (CIs) and were analysed using an intention-to-treat principle. Main results and the role of chance Six retrospective studies (n = 11,685) published between 2018 and 2024 with moderate-to-low risk of bias were analysed. Sample size ranged from 127 to 3,372 patients. • Clinical pregnancy rates were lower in patients with dyslipidaemia compared to those without (RR 0.85, 95% CI 0.74–0.99; random effects model; I² 73.4%; five studies, 5,477 patients). • Dyslipidaemia was associated with higher miscarriage rate (RR 1.24, 95% CI 1.01–1.53; fixed effects model, I²: 0%; four studies, 5,019 patients) compared with normal lipid profile. • Patients with dyslipidaemia had lower live birth rates compared to those without (RR 0.82, 95% CI 0.68–0.99; random effects model; I² 89.4%; three studies, 4,972 patients). • No differences were noted in cumulative live birth rates between the two groups (RR 0.98, 95% CI 0.94–1.02; fixed effects model, I² 0%; two studies, 5,834 patients). Limitations, reasons for caution This analysis included a limited number of retrospective studies with moderate-to-low risk of bias due to methodological limitations. Considerable heterogeneity in terms of the population studied, criteria for dyslipidaemia definition and embryo transfer types necessitates cautious interpretation of findings. Wider implications of the findings This systematic review and meta-analysis is the first performed so far on this topic, showing decreased pregnancy outcomes in women with dyslipidaemia compared to those without. This underscores the importance of lipid profile screening before infertility treatment and necessitates prompt lifestyle intervention to reduce this effect. Trial registration number No

Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation.

BackgroundRecent studies have consistently shown that AFC and serum AMH are good predictors of ovarian response and have shown strong correlations. However, it is not unusual for reproductive medicine specialists to encounter discordance between them. This is the first study to investigate the efficacies of the different COS protocols when the AFC and AMH levels are discordant. Based on the association between COS protocols and pregnancy outcomes, we attempt to explain the controversial results and clarify the predictive value of AMH and AFC in this context.Methods19,239 patients undergoing their first fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles with GnRH antagonist protocols, GnRH-a long protocols or GnRH-a ultra-long protocols between January 1, 2016, and December 31, 2019, were enrolled and then divided into four groups in accordance with the boundaries for the AFC and serum AMH level provided by the Poseidon Classification. Our study was divided into two parts. Firstly, we retrospectively compared the effects of the three COS protocols in patients with discordant AMH and AFC. Multivariate logistic regression models were conducted in a forward manner to exclude the influence of confounding factors. Afterward, to increase comparability between Group 2 (low AMH and normal AFC) and Group 3 (normal AMH and low AFC), propensity score matching (PSM) analysis was performed based on age, BMI, the number of embryos transferred, and COS protocol. IVF intermediate and reproductive outcomes were compared between Group 2 and Group 3.ResultsFor people with low AMH and normal AFC (Group 2), the number of total oocytes, clinical pregnancy rate (CPR), live birth rate (LBR) and cumulative live birth rate (CLBR) were significantly higher in GnRH-a ultra-long protocol compared with GnRH antagonist protocol. In multivariate logistic regression models, significant associations of COS protocol with fresh LBR and CPR were found after adjusting for age, BMI, AFC, AMH and the number of embryos transferred. Whereas, in patients with normal AMH and low AFC (Group 3), the number of total oocytes, CLBR, LBR and CPR were highest in the long GnRH-a protocol although there was no statistically significant difference. After PSM, the results showed that although oocytes yield and available embryos in patients with normal AMH and low AFC were significantly higher, there was no significant difference in reproductive outcomes between Group 2 and Group 3.ConclusionsWe found that women with normal AFC and low AMH may benefit from the GnRH-a ultra-long protocol. Nevertheless, for women with normal AMH and low AFC, the long GnRH-a protocol seems to be associated with better clinical outcomes. Furthermore, after eliminating the confounding factors including the COS protocol, we found that AMH can only predict the number of oocytes but not the quality of oocytes when there was discordance between AFC and AMH.

Reducing radicality in fertility-sparing surgery is associated with improved in vitro fertilization outcome in early-stage cervical cancer: A national retrospective study

Does surgery for colorectal endometriosis prior to IVF±ICSI have an impact on cumulative live birth rates?

Oocyte retrieval versus conversion to intrauterine insemination in patients with poor response to gonadotropin therapy

To investigate the clinical outcomes of conventional IVF and ICSI in female patients aged 40years and over with no more than five oocytes retrieved and non-male factor infertility. A retrospective study of a cohort of 644 patients undergoing IVF/ICSI treatment. The 534 female patients aged ≧ 40years with no more than five oocytes retrieved and non-male factor infertility undergoing their first conventional IVF cycles were assigned in IVF group. The rest of 110 patients aged 40years and over with no more than five oocytes retrieved and non-male factor infertility undergoing first ICSI cycles were recruited in ICSI group. Our results showed the clinical pregnancy, live birth and miscarriage rates were similar between the IVF and ICSI groups (21.59% vs. 13.25%, P>0.05; 12.16% vs. 6.02%, P>0.05; 43.68% vs. 54.55%, P>0.05; respectively), however, the implantation and cumulative live-birth rates were significantly higher in the IVF compared to the ICSI group (15.11% vs. 7.75%, 14.59% vs. 5.56%, P<0.05), though the IVF group had a lower normal fertilization rate (61.56% vs. 76.00%, P<0.001). Our study provides strong evidences that the conventional IVF exhibits advantages over the ICSI method in non-male factor infertility for advanced age patients with five or fewer oocytes retrieved.

Does the time elapsed between oocyte pick-up (OPU) and denudation or injection affect the probability of achieving a live birth (LB) in ICSI cycles? Prolonged oocyte culture before denudation (>4 h) was associated with an increase in clinical pregnancy (CP), LB and cumulative LB (CLB) rates when compared with earlier denudation timings. Oocyte maturation is a complex and dynamic process involving structural and biochemical modifications in the cell necessary to support fertilization and early embryo development. While meiotic competence is easily identifiable by the presence of an extruded first polar body, cytoplasmic maturation cannot be assessed microscopically. Culturing oocytes with their surrounding cumulus cells (CCs) prior to ICSI can enhance the completion of in vitro cytoplasmic maturation; conversely, prolonged culture may induce cell degeneration. The optimal culture intervals prior to oocyte denudation and/or injection have not yet been established and may prove relevant for the improvement of ICSI reproductive outcomes. This is a single-centre retrospective cohort analysis of 1378 ICSI cycles performed between January 2005 and October 2018. Data were categorized according to: (i) the time interval between OPU and denudation (<3 h, 3-4 h and ≥4 h), (ii) the time interval between denudation and ICSI (<1.5 h, 1.5-2 h, ≥2 h) and (iii) the time interval between OPU and ICSI (<5 h, 5-6 h and ≥6 h). The effect of these timings on fertilization, CP, LB and CLB rates were compared. The culture intervals between different procedures were dependent exclusively on laboratory workload. ICSI cycles performed in women younger than 40 years old using autologous gametes with at least one metaphase II injected oocyte were included. The effect of oocyte culture duration prior to denudation and injection of the oocytes was compared using multivariable regression accounting for potential confounding variables. Fertilization and oocyte damage rate after ICSI was found to be independent of the time interval to denudation (<3 h, 3-4 h and ≥4 h) and/or injection (<5 h, 5-6 h and ≥6 h). Extending oocyte culture before denudation significantly improved CP (29.5%, 42.7% and 50.6%, respectively), LB (25.1%, 34.4% and 40.7%, respectively) and CLB rates (26.0%, 36.1% and 42.2%, respectively), particularly if the time interval was at least 4 h. Additionally, LB (31.7%, 35.8% and 27.4%, respectively) and CLB rates (34.2%, 36.6% and 27.7%, respectively) were also dependent on the time from OPU to injection. This study is limited by its retrospective nature and potential unmeasured confounding cannot be excluded. Furthermore, the effect of even shorter or longer periods of culture before denudation and/or injection were not evaluated and should not be extrapolated from these results. Our findings propose new evidence of a previously unrecognized protective effect of the CCs-oocyte interactions in human ART, raising the question of a possible downstream effect in embryogenesis which significantly affects LB rates. Additionally, this is the first study to suggest a negative effect of further extending culture before ICSI on LB and CLB rates, thus potentially allowing for the narrowing of an optimal ICSI time interval. Simple strategies such as the establishment of more effective time frames to perform these procedures and adjusting laboratory practice may prove beneficial, ultimately improving ICSI reproductive outcomes. None. N/A.

The clinical effect of sperm DNA damage in assisted reproduction has been a controversial topic during recent decades, leading to a variety of clinical practice recommendations. While the latest European Society of Human Reproduction and Embryology (ESHRE) position report concluded that DNA damage negatively affects assisted reproduction outcomes, the Practice Committee of the American Society for Reproductive Medicine (ASRM) does not recommend the routine testing of DNA damage for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Herein, our aim was to perform a systematic review and meta-analysis of studies investigating whether sperm DNA damage affects clinical outcomes in IVF and ICSI, in order to contribute objectively to a consistent clinical recommendation. A comprehensive systematic search was conducted according to PRISMA guidelines from the earliest available online indexing year until March 2020, using the MEDLINE-PubMed and EMBASE databases. We included studies analysing IVF and/or ICSI treatments performed in infertile couples in which sperm DNA damage was well defined and assessed. Studies also had to include information about pregnancy, implantation or live birth rates as primary outcomes. The NHLBI-NIH quality assessment tool was used to assess the quality of each study. Meta-analyses were conducted using the Mantel-Haenszel method with random-effects models to evaluate the Risk Ratio (RR) between high-DNA-damage and control groups, taking into account the 95% confidence intervals. Heterogeneity among studies was evaluated using the I2 statistic. We also conducted sensitivity analyses and post-hoc subgroup analyses according to different DNA fragmentation assessment techniques. We identified 78 articles that met our inclusion and quality criteria and were included in the qualitative analysis, representing a total of 25639 IVF/ICSI cycles. Of these, 32 articles had sufficient data to be included in the meta-analysis, comprising 12380 IVF/ICSI cycles. Meta-analysis revealed that, considering IVF and ICSI results together, implantation rate (RR=0.74; 95% CI=0.61-0.91; I2 = 69) and pregnancy rate (RR=0.83; 0.73-0.94; I2 = 58) are negatively influenced by sperm DNA damage, although after adjustment for publication bias the relationship for pregnancy rate was no longer significant. The results showed a non-significant but detrimental tendency (RR=0.78; 0.58-1.06; I2 = 72) on live birth rate. Meta-analysis also showed that IVF outcomes are negatively influenced by sperm DNA damage, with a statistically significant impact on implantation (RR=0.68; 0.52-0.89; I2 = 50) and pregnancy rates (RR=0.72; 0.55-0.95; I2 = 72), although the latter was no longer significant after correction for publication bias. While it did not quite meet our threshold for significance, a negative trend was also observed for live birth rate (RR=0.48; 0.22-1.02; I2 = 79). In the case of ICSI, non-significant trends were observed for implantation (RR=0.79; 0.60-1.04; I2 = 72) or pregnancy rates (RR=0.89; 0.78-1.02; I2 = 44), and live birth rate (RR=0.92; 0.67-1.27; I2 = 70). The current review provides the largest evidence to date supporting a negative association between sperm DNA damage and conventional IVF treatments, significantly reducing implantation and pregnancy rates. The routine use of sperm DNA testing is therefore justified, since it may help improve the outcomes of IVF treatments and/or allow a given couple to be advised on the most suitable treatment. Further well-designed controlled studies on a larger number of patients are required to allow us to reach more precise conclusions, especially in the case of ICSI treatments.

Background Borderline ovarian tumours account for 10–20% of all epithelial ovarian tumours. As one-third of these tumours are seen in women less than 40 years of age, fertility remains a major concern in their management. Conservative surgery has been advocated in these cases. Fertility treatment has been successfully used in some of these cases with good results. However, the risk of tumour recurrence cannot be ignored. Case report A young nulliparous woman had fertility sparing surgery (bilateral salpingo-oophorectomy and omentectomy) for serous borderline ovarian tumours with noninvasive implants (stage IIIc). After 10 years of uneventful follow-up, she decided to undergo an in-vitro fertilization with donor oocytes. She received unopposed oestrogen stimulation for 12 days to prime the endometrium and developed ascites. Subsequent investigations revealed tumour recurrence in the form of low-grade serous adenocarcinoma. The carcinoma proved resistant to chemotherapy and pursued an aggressive course culminating in death within 6 months of diagnosis. Conclusion Borderline ovarian tumours can recur in an aggressive manner even after a prolonged follow-up. Large clinical trials with longer follow-up are needed to evaluate the safety of controlled ovarian hyperstimulation after conservative surgery for borderline ovarian tumours.

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) treatment has included ultrasonography plus serum estradiol concentration to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS). The need for intensive monitoring during ovarian stimulation in IVF is controversial. It has been suggested that close monitoring is time consuming, expensive and inconvenient for the woman and simplification of IVF therapy by using ultrasound only should be considered. This systematic review assessed the effects of ovarian monitoring by ultrasound only versus ultrasound plus serum estradiol measurement on IVF outcomes and the occurrence of OHSS in women undergoing stimulated cycles in IVF and intra-cytoplasmic sperm injection (ICSI) treatment. To quantify the effect of monitoring controlled ovarian stimulation in IVF and ICSI cycles with ultrasound plus serum estradiol concentration versus ultrasound only in terms of live birth rates, pregnancy rates and the incidence of OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) on the latest issue of The Cochrane Library, MEDLINE (1966 to May 2007), EMBASE (1980 to May 2007), CINAHL (1982 to May 2007), the National Research Register, and web-based trial databases such as Current Controlled Trials. There was no language restriction. Additionally all references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with ultrasound plus serum estradiol concentration versus ultrasound only in women undergoing ovarian hyperstimulation for IVF and ICSI treatment were included. Two review authors independently examined the electronic search results for relevant trials, extracted data and assessed trial quality. They resolved disagreements by discussion with two other authors. Outcomes data were pooled when appropriate and summary statistics presented when limited data did not allow meta-analysis. Our search strategy identified 1119 potentially eligible reports, of which two met our inclusion criteria. These involved 411 women who underwent controlled ovarian stimulation monitoring. Our primary outcome of live birth rate was not reported in either study. One trial reported clinical pregnancy rate per woman (33% versus 31%; RR 1.07, 95% CI 0.77 to 1.49), the second trial reported clinical pregnancy rate per oocyte retrieval (22% versus 25%). There was no significant difference between the ultrasound plus estradiol group and the ultrasound alone group in the mean number of oocytes retrieved (WMD -0.55, 95% CI -1.79 to 0.69) and the incidence of ovarian hyperstimulation (RR 0.73, 95% CI 0.30 to 1.78) for the two studies. There is no evidence from randomised trials to support cycle monitoring by ultrasound plus serum estradiol as more efficacious than cycle monitoring by ultrasound only on outcomes of live birth and pregnancy rates. A large well-designed randomised controlled trial is needed that reports on live birth rates and pregnancy, with economic evaluation of the costs involved and the views of the women undergoing cycle monitoring. A randomised trial with sufficiently large sample size to test the effects of different monitoring protocols on OHSS, a rare outcome, will pose a great challenge. Until such a trial is considered feasible, cycle monitoring by transvaginal ultrasound plus serum estradiol may need to be retained as a precautionary good practice point.

During the last decades, many studies have shown the possible influence of sperm DNA fragmentation on assisted reproductive technique outcomes. However, little is known about the impact of sperm DNA fragmentation on the clinical outcome of frozen-thawed embryo transfer (FET) from cycles of conventional in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI). In the present study, the relationship between sperm DNA fragmentation (SDF) and FET clinical outcomes in IVF and ICSI cycles was analyzed. A total of 1082 FET cycles with cleavage stage embryos (C-FET) (855 from IVF and 227 from ICSI) and 653 frozen-thawed blastocyst transfer cycles (B-FET) (525 from IVF and 128 from ICSI) were included. There was no significant change in clinical pregnancy, biochemical pregnancy and miscarriage rates in the group with a SDF >30% compared with the group with a SDF ≤30% in IVF and ICSI cycles with C-FET or B-FET. Also, there was no significant impact on the FET clinic outcome in IVF and ICSI when different values of SDF (such as 10%, 20%, 25%, 35%, and 40%) were taken as proposed threshold levels. However, the blastulation rates were significantly higher in the SDF ≤30% group in ICSI cycle. Taken together, our data show that sperm DNA fragmentation measured by Sperm Chromatin Dispersion (SCD) test is not associated with clinical outcome of FET in IVF and ICSI. Nonetheless, SDF is related to the blastocyst formation in ICSI cycles.

Study question Does recombinant luteinizing hormone (r-LH) supplementation improve cumulative live birth rates (CLBR) in overweight/obese women undergoing in vitro fertilization (IVF)? Summary answer In overweight/obese women undergoing in IVF, recombinant follicle-stimulating hormone (r-FSH) supplementation with r-LH did not significantly improve CLBR or pregnancy outcomes compared to r-FSH alone. What is known already Female obesity is strongly associated with impaired fertility and adverse pregnancy outcomes.A small retrospective study involving 208 overweight/obese non-PCOS patients found a higher number of high-quality embryos after adding LH during ovarian stimulation, however, live birth rates were not reported. It remains unclear whether LH supplementation improves the clinical outcomes in IVF for overweight/obese women. As CLBR is the most patient-centered outcome, we aimed to investigate the effect of r-LH supplementation on CLBR in overweight and obese women undergoing IVF. Study design, size, duration This was a retrospective cohort study conducted at the Center for Clinical Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University. Clinical data of patients who underwent IVF from 2013 to 2021 were analyzed and the follow-up time was extended to 2023. Participants/materials, setting, methods Patients were divided into two groups based on whether they received r-LH supplementation from the first day of gonadotropin initiation: r-FSH/r-LH and r-FSH alone. A total of 791 oocyte retrieval cycles were included and categorized into r-FSH/r-LH group and r-FSH group. Propensity score matching (PSM) for potential confounders was performed in a 1:1 ratio. The primary outcome was CLBR. Main results and the role of chance The baseline characteristics of the two groups were comparable after PSM. Total gonadotropin dose was significantly higher in r-FSH/r-LH group compared with r-FSH group (1800IU versus 1600IU, P &amp;lt; 0.001). However, patients in r-FSH/r-LH group had lower estradiol levels on trigger day (12332.95 pmol/L versus 15881.00 pmol/L, P = 0.007) and fewer oocytes retrieved (10 versus 11, P = 0.029). There were no significant differences in biochemical pregnancy rate, clinical pregnancy rate, miscarriage rate, and live birth rate between the two groups after the first embryo transfer. The CLBR was also similar (85% versus 94%, P = 0.228). The results remained consistent after adjusting for potential confounders such as total gonadotropin dose, estradiol level on the trigger day, and number of oocytes retrieved by logistic regression. There were no significant differences in obstetric-perinatal complications. Limitations, reasons for caution This is a single-center retrospective study, there may be a selection bias of LH supplementation. In addition, the sample size of this study was relatively small because the timing of LH supplementation was synchronized with the day of gonadotropin initiation. Wider implications of the findings In overweight/obese women undergoing IVF, r-FSH supplementation with r-LH did not significantly improve CLBR or pregnancy outcomes compared to r-FSH alone. Our findings provide valuable evidence for optimizing ovarian stimulation strategies in this population. Based on our data, routine rLH supplementation may not be recommended for these women. Trial registration number Yes