Co-Administration of Clomiphene Citrate and Letrozole in Mild Ovarian Stimulation Versus Conventional Controlled Ovarian Stimulation Among POSEIDON Group 4 Patients

This retrospective study assessed the effect of the co-administration of clomiphene citrate (CC) and letrozole in mild ovarian stimulation, compared to conventional regimens, among Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 4 patients. There were 114 POSEIDON Group 4 patients undergoing in vitro fertilization treatments with 216 stimulation cycles recruited from a Taiwan’s reproductive center during 2016-2020. Main outcomes were the numbers, quality of retrieved oocytes and embryo development. Pregnancy outcomes were assessed after embryo transfers. Per stimulation cycle, patients receiving mild stimulation with a combination of CC and letrozole (study group) versus those with COS (control group) had lower numbers of pre-ovulatory follicles (2.00 ± 1.23 vs. 2.37 ± 1.23, p=0.0066) and oocytes retrieved (1.83 ± 1.17 vs. 2.37 ± 1.23, p=0.0017), and lower follicular output rate (58.6% vs. 68.38%, p=0.0093) and mature oocyte output rate (44.29% vs. 52.88%, p=0.0386) but a higher top-quality metaphase II oocyte ratio (66.7% vs. 54.59%, p=0.0444) and a similar fertilization rate (91.67% vs. 89.04%, p=0.4660). With adjustment for significant between-group baseline differences using multivariable logistic generalized estimating equation model analyses, there was no statistical difference in oocytes retrieved and embryo development between the study and control groups, and insignificant increases in successful pregnancies in the study group were found compared to the control group (i.e., odds ratios [95% CIs]: 1.13 [0.55, 232] and 1.50 [0.65, 3.49] for ongoing pregnancy and live birth, respectively). For POSEIDON Group 4 patients, cotreatment of CC and letrozole in mild stimulation may increase the high-quality oocyte ratio and yield comparable fertilization rate and pregnancy outcomes.

P–635 Standard versus mild ovarian stimulation in women with polycystic ovaries (PCO): Impact on outcomes in subsequent frozen embryo treatment cycles (FET)

Study question Does mild ovarian stimulation in women with PCO result in higher live birth rates during subsequent FET cycles? Summary answer Mild ovarian stimulation with FSH doses <150IU did not result in higher clinical pregnancy or livebirth rates in subsequent FET. What is known already Ovarian stimulation during IVF in women with PCO is associated with an exaggerated response, ovarian hyperstimulation syndrome, poor egg to follicle ratio, low fertilisation rates and poor blastocyst conversion. Mild ovarian stimulation, often referred to as protocols with FSH doses under 150IU, is often employed to overcome these challenges. One of the perceived benefits of this approach is improved oocyte and embryo quality reflected in lower aneuploidy rates. Study design, size, duration This was a retrospective observational study looking at 99 FET between January 2011 and Jan 2021 that followed a fresh cycle in women with a pre-treatment antral follicle count of 12 + 12 or greater. Patients were identified through the antral follicle count at the pre-treatment investigation ultrasound scan. Ultrasound findings, treatment cycle details and clinical outcomes were entered prospectively into a dedicated clinic database. Data was retrieved and analysed using SPSS V25. Participants/materials, setting, methods The study was conducted in a large IVF centre. Data on women with an AFC of 12 + 12 or above, undergoing an autologous FET cycle following a fresh cycle were collected. Women were split into those receiving <150IU of FSH (Group1, n = 51) and those receiving FSH ³150 IU (Group 2, n = 48). Binary logistic regression analysis was performed to control for confounders. Live birth was the primary outcome, with biochemical and clinical pregnancy being secondary outcomes. Main results and the role of chance Women in Group 1 were younger (30.8±3.6 v 33.8±3.65, p < 0.005) but had a similar antral follicle count (38.2±11.7 v 34.2±9.1, p = 0.07). The total number of eggs collected (24.1±13.8 v 25.9±8.8, p = 0.45) and fertilisation rate (0.59±0.2 v 0.58±0.18, p = 0.77) during their fresh cycle were comparable. Women in Group 2 had a larger number of embryos suitable for cryopreservation (7.36±4.2 v 4.8±3.5, p = 0.001) In the subsequent frozen embryo replacement cycle, there was no difference in the number or quality of embryos transferred with most women having a single embryo transfer (63% v 48%, p = 0.14) and at least one top quality embryo transferred (68.6% v 81%, p = 0.15). There was a higher biochemical pregnancy rate in Group 1 (84% v 66%, p = 0.035) but with no difference in clinical pregnancy rate (53% v 44%, p = 0.37) or live birth rate (49% v 42%, p = 0.76). Live birth rates remained comparable even after controlling for age, and number and quality of embryos transferred (OR: 1.21 (95% CI 0.50–2.94). Limitations, reasons for caution This was a retrospective analysis raising the risk of allocation bias. This study was also at risk of information bias as it relied on accurate documentation of the AFC at the pre-treatment scan. Wider implications of the findings: Patients can be reassured that both stimulation protocols result in similar live birth rates in subsequent frozen embryo replacement cycles. Prospective trials using PGT-A are required to assess whether aneuploidy could account for the discrepancy in biochemical pregnancy rates in the two groups considering the subsequent comparable clinical pregnancy rates. Trial registration number Not applicable

SAY NO to mild ovarian stimulation for all poor responders: it is time to realize that not all poor responders are the same

ABSTRACT Over the last 25 years, a vast body of literature has been published evaluating different treatment modalities for the management of poor ovarian responders. Despite the evidence that maximizing ovarian response can improve the chances of live born babies in poor responders, there are still voices suggesting that all poor responders are the same, irrespective of their age and their actual ovarian reserve. This has resulted in the suggestion of adopting a mild ovarian stimulation approach for all poor responders, based on the results of several trials which failed to identity differences when comparing mild and more intense stimulation in predicted poor responders. The current article analyzes in detail these studies and discusses the shortcomings in terms of type of population included, outcomes and settings performed, which may actually be responsible for the belief that only mild stimulation should be used. In the era of individualization in medicine, it must be realized that there are subgroups of predicted poor responders who will benefit from an individual rather than ‘one fits all’ mild stimulation approach and thus we should provide the same standard of treatment for all our poor responder patients.