Cumulative live birth rate following ovarian stimulation with freeze-all in women with polycystic ovaries: does the PCOS phenotype have an impact?

Author(s):  
S. Mackens ◽  
P. Drakopoulos ◽  
M.F. Moeykens ◽  
L. Mostinckx ◽  
L. Boudry ◽  
...  
2019 ◽  
Vol 26 (1) ◽  
pp. 119-136 ◽  
Author(s):  
Yossi Mizrachi ◽  
Eran Horowitz ◽  
Jacob Farhi ◽  
Arieh Raziel ◽  
Ariel Weissman

Abstract BACKGROUND Freeze-all IVF cycles are becoming increasingly prevalent for a variety of clinical indications. However, the actual treatment objectives and preferred treatment regimens for freeze-all cycles have not been clearly established. OBJECTIVE AND RATIONALE We aimed to conduct a systematic review of all aspects of ovarian stimulation for freeze-all cycles. SEARCH METHODS A comprehensive search in Medline, Embase and The Cochrane Library was performed. The search strategy included keywords related to freeze-all, cycle segmentation, cumulative live birth rate, preimplantation genetic diagnosis, preimplantation genetic testing for aneuploidy, fertility preservation, oocyte donation and frozen-thawed embryo transfer. We included relevant studies published in English from 2000 to 2018. OUTCOMES Our search generated 3292 records. Overall, 69 articles were included in the final review. Good-quality evidence indicates that in freeze-all cycles the cumulative live birth rate increases as the number of oocytes retrieved increases. Although the risk of severe ovarian hyperstimulation syndrome (OHSS) is virtually eliminated in freeze-all cycles, there are certain risks associated with retrieval of large oocyte cohorts. Therefore, ovarian stimulation should be planned to yield between 15 and 20 oocytes. The early follicular phase is currently the preferred starting point for ovarian stimulation, although luteal phase stimulation can be used if necessary. The improved safety associated with the GnRH antagonist regimen makes it the regimen of choice for ovarian stimulation in freeze-all cycles. Ovulation triggering with a GnRH agonist almost completely eliminates the risk of OHSS without affecting oocyte and embryo quality and is therefore the trigger of choice. The addition of low-dose hCG in a dual trigger has been suggested to improve oocyte and embryo quality, but further research in freeze-all cycles is required. Moderate-quality evidence indicates that in freeze-all cycles, a moderate delay of 2–3 days in ovulation triggering may result in the retrieval of an increased number of mature oocytes without impairing the pregnancy rate. There are no high-quality studies evaluating the effects of sustained supraphysiological estradiol (E2) levels on the safety and efficacy of freeze-all cycles. However, no significant adverse effects have been described. There is conflicting evidence regarding the effect of late follicular progesterone elevation in freeze-all cycles. WIDER IMPLICATIONS Ovarian stimulation for freeze-all cycles is different in many aspects from conventional stimulation for fresh IVF cycles. Optimisation of ovarian stimulation for freeze-all cycles should result in enhanced treatment safety along with improved cumulative live birth rates and should become the focus of future studies.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Kenji Ezoe ◽  
Xiaowen Ni ◽  
Tamotsu Kobayashi ◽  
Keiichi Kato

Abstract Background Several studies have investigated the correlation between the serum anti-Müllerian hormone (AMH) level and in vitro fertilization (IVF) outcomes in controlled ovarian stimulation cycles; however, studies regarding the correlation of the serum AMH level with IVF outcomes in minimal ovarian stimulation cycles remain limited. In this study, we aimed to analyze the correlation of the serum AMH level with ovarian responsiveness, embryonic outcomes, and cumulative live birth rates in clomiphene citrate (CC)-based minimal ovarian stimulation cycles. Methods Clinical records of 689 women whose entire ovarian stimulation regimen consisted solely of minimal stimulation cycle IVF using CC alone from November 2017 to October 2019 were retrospectively reviewed. The association between IVF outcomes and the serum AMH level before the initiation of the first fertility treatment was analyzed. Furthermore, the correlation of the serum AMH level with cumulative live birth rates after IVF treatment was assessed. The Cochran-Armitage test, Pearson’s chi-squared test, Spearman rank correlation test, Student’s t-test, one-way analysis of variance, logistic regression analysis, Kaplan-Meier method and Cox proportional hazards model were used to analyze the data. Results The serum AMH level positively correlated with the number of retrieved oocytes, blastocyst formation rate, blastocyst cryopreservation rate, and live birth rate per oocyte retrieval in CC-based minimal ovarian stimulation cycles without any exogenous gonadotropin administration. Furthermore, the cumulative live birth rate and treatment period required for conceiving were strongly associated with the serum AMH level at the initiation of fertility treatment. Conclusions A low serum AMH level correlated with low ovarian responsiveness, impaired pre-implantation embryonic development, and decreased cumulative live birth rate in CC-based minimal ovarian stimulation cycles. Therefore, the cycle success rate would be predicted by measuring the serum AMH level in minimal ovarian stimulation with CC alone.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fumei Gao ◽  
Yanbin Wang ◽  
Dan Wu ◽  
Min Fu ◽  
Qiuxiang Zhang ◽  
...  

This is a retrospective cohort study included 1021 patients underwent a flexible GnRH antagonist IVF protocol from January 2017 to December 2017 to explore the effect of a premature rise in luteinizing hormone (LH) level on the cumulative live birth rate. All patients included received the first ovarian stimulation and finished a follow-up for 3 years. A premature rise in LH was defined as an LH level >10 IU/L or >50% rise from baseline during ovarian stimulation. The cumulative live birth rate was calculated as the number of women who achieved a live birth divided by the total number of women who had either delivered a baby or had used up all their embryos received from the first stimulated cycle. In the advanced patients (≥37 years), the cumulative live birth rate was reduced in patients with a premature rise of LH (β: 0.20; 95% CI: 0.05–0.88; p=0.03), compared to patients (≥37 years) without the premature LH rise. The incidence of premature LH rise is associated with decreased rates of cumulative live birth rate in patients of advanced age (≥37 years) and aggravated the reduced potential of embryos produced by the advanced age, not the number of embryos.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M De Vos ◽  
P Drakopoulos ◽  
M F Moeykens ◽  
L Mostinckx ◽  
I Segers ◽  
...  

Abstract Study question Do cumulative live birth rates (CLBR) differ between PCOS phenotypes when a freeze-all strategy is used to prevent OHSS after ovarian stimulation (OS)? Summary answer When conventional-dose OS resulted in high response, a CLBR of ∼ 70% was observed after “freeze-all” in women with PCOS, irrespective of their phenotype. What is known already Previous observational studies have shown that CLBR in women with PCOS who undergo assisted reproductive technologies (ART) may depend on their phenotype. When OS was performed with caution to avoid ovarian hyperresponse, CLBR was lower in women with a hyperandrogenic PCOS phenotype. However, when women with PCOS do exhibit hyperresponse and a freeze-all strategy is used, the impact of the PCOS phenotype on the clinical outcome of the ART cycle is unclear. Study design, size, duration This is a single-centre, retrospective cohort study including 422 women with polycystic ovary syndrome (PCOS) as defined by Rotterdam criteria or PCO-like ovarian morphology-only (PCOM) in whom a freeze-all strategy was applied after GnRH agonist triggering in the context of hyperresponse defined as ³19 follicles of ³11mm in their first or second IVF-ICSI cycle between January 2015 and December 2019 in a tertiary referral hospital. Participants/materials, setting, methods PCOS phenotype was based on hyperandrogenism (H), ovulatory dysfunction (O) and PCO-like ovarian morphology (P). Ovarian stimulation was performed with rFSH or HPhMG, adjusted to BMI. The primary outcome was cumulative live birth rate (CLBR) resulting from the transfer of all cryopreserved embryos from the same IVF-ICSI cycle. Patient and cycle characteristics and laboratory and clinical data were analysed. Data were analysed by multivariate logistic regression adjusting for covariates. Main results and the role of chance In total, 91/422 (21.6%) patients had PCOS phenotype A (HOP); 33 (7.8%) had phenotype C (HP), 161/422 (38.2%) had phenotype D (OP) and 137/422 (32.5%) had PCOM (n = 137). BMI, AMH and AFC were significantly different between phenotype groups (p < 0.001), and highest in PCOS phenotype A. The type of gonadotropin used, as well as the mean daily and total stimulation dose were comparable for all groups. The mean number of retrieved oocytes was comparable among groups (22.4±10.8 for phenotype A, 21.4±7.1 for phenotype C, 20.4±7.8 for phenotype D and 22.2±9.7 for PCOM; p = 0.46). The mean number of embryos available for vitrification differed significantly (4.4±3.7, 5.7±3.4, 5.7±3.4 and 5.2±3.6, respectively; p = 0.005). Following the first frozen embryo transfer, LBR was comparable among groups (41.5%, 43.3%, 49.3% and 38.5%, respectively; p = 0.31). Unadjusted CLBR was also similar (69.2%, 69.7%, 79.5% and 67.9%, respectively; p = 0.11). The multivariate logistic regression model adjusting for age, BMI, number of oocytes and embryo stage (cleavage vs. blastocyst stage) confirmed that the PCOS/PCOM phenotype did not have any impact on CLBR (OR 0.80, CI 0.28-2.29 (phenotype C); OR 1.40, CI 0.67-2.90 (phenotype D); OR 0.65, CI 0.31-1.34 (PCOM); p = 0.1, with phenotype A as reference). Limitations, reasons for caution These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors. The results cannot be generalised to all ART cycles in women with polycystic ovaries as they pertain to those cycles where OS leads to hyperresponse. Wider implications of the findings In subfertile women with PCOS eligible for ART, hyperresponse after OS confers excellent cumulative live birth rates when a freeze-all strategy is used, eliminating unfavourable clinical outcomes that had previously been observed in hyperandrogenic PCOS women after mild OS targeting normal ovarian response and fresh embryo transfer. Trial registration number not applicable


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