Factors Contributing to Good Oocyte Competence and Utility Rates for In Vitro Fertilization or Intracytoplasmic Sperm Injection in High Responders
The oocyte utility rate (OUR) is a critical metric in assisted reproductive technology (ART), reflecting the competence of oocytes to develop into usable embryos that can be transferred or cryopreserved. While maternal age is a well-known factor influencing oocyte quality, other intra-ovarian and extra-ovarian factors can significantly impact the interaction between oocytes and granulosa cells, oocyte maturation, and subsequent zygote development. This study aimed to identify the factors contributing to the disparity between high and low OUR in high responders undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The findings provide valuable insights for optimizing IVF outcomes in this patient population.
The study analyzed IVF/ICSI cycles performed at a single institution between January 1, 2013, and December 31, 2019. Cycles with at least 15 retrieved oocytes were included, and no fresh embryo transfers were performed to mitigate the risk of ovarian hyperstimulation syndrome (OHSS). The OUR was defined as the number of applicable embryos (both blastomeres and blastocysts) divided by the number of oocytes retrieved in a given cycle. The cycles were ranked based on their OUR, with the highest 10% classified as Group A (high OUR) and the lowest 10% as Group B (low OUR).
The ovarian stimulation protocols included the gonadotropin-releasing hormone (GnRH) agonist long protocol, GnRH antagonist protocol, and dual suppression protocol. The starting dose of recombinant follicle-stimulating hormone (rFSH) was determined based on the patient’s age, body mass index (BMI), and ovarian reserve test results. Oocyte maturation was triggered using human chorionic gonadotropin (hCG), and oocytes were collected 36 hours later. Embryo development was assessed on day 3 and day 5 or 6. On day 3, two top-grade embryos were vitrified, while the remaining embryos were cultured to blastocysts and cryopreserved.
A total of 453 patients were included in the study, with 43 in Group A and 47 in Group B. The two groups did not differ significantly in age, BMI, infertility duration, or basal hormone levels. However, Group B had a higher proportion of patients with ovulatory disorders or endometriosis, and ICSI was used more frequently in this group (34% vs. 14% in Group A). Notably, a higher proportion of patients in Group B experienced a decline in estradiol (E2) levels during the stimulation process, and 44.7% of cycles in Group B had rFSH suspended before the trigger day. Despite similar numbers of retrieved oocytes and metaphase II (MII) oocytes, the developmental potential of oocytes differed significantly between the groups.
On day 3, 15.8% of embryos in Group A were of good quality, compared to only 3.7% in Group B. Group A also had a higher number of eight-cell blastomeres. Although both groups had similar numbers of embryos cultured to blastocysts, Group B had a significantly lower blastocyst formation rate (78.1% vs. 7.9%). Group A had an average of 14 embryos cryopreserved per cycle, while Group B had only 2. In frozen-thawed cycles, Group A achieved a cumulative clinical pregnancy rate of 95.3% and a cumulative live birth rate of 90.7%, compared to 31.9% and 40.4%, respectively, in Group B.
Logistic regression analysis was performed to identify factors influencing OUR. Previous IVF/ICSI attempts (odds ratio [OR]: 0.10, 95% confidence interval [CI]: 0.01–0.81), infertility due to endometriosis (OR: 0.16, 95% CI: 0.03–0.84), and decreased E2 levels during stimulation (OR: 0.16, 95% CI: 0.04–0.64) were associated with poorer OUR. Conversely, longer ovarian stimulation durations (OR: 3.24, 95% CI: 1.25–8.42) were linked to better OUR. Compared to the GnRH agonist long protocol, the GnRH antagonist protocol (OR: 1.39, 95% CI: 1.09–10.04) and dual suppression protocol (OR: 3.74, 95% CI: 1.06–26.86) were associated with higher OUR.
The study highlighted that previous IVF/ICSI cycles may negatively impact OUR, potentially due to suboptimal luteal phase support or stimulation protocols. A decline in E2 levels during stimulation was also identified as a risk factor for reduced OUR, particularly in high responders. This finding contrasts with some previous studies that found no significant impact of E2 decline on live birth rates, but those studies included normal and poor responders rather than high responders. The multifactorial analysis confirmed that endometriosis poses a significant threat to OUR, likely due to impaired oocyte competence and fertilization rates.
For high responders, the dual suppression protocol and the use of oral contraceptives before the GnRH agonist long protocol were associated with improved OUR. These approaches are particularly beneficial for patients with polycystic ovary syndrome (PCOS), as they help regulate the luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio and reduce serum dehydroepiandrosterone sulfate (DHEAS). Additionally, dual suppression has been shown to prevent OHSS without compromising endometrial thickness or oocyte quality.
In conclusion, this study provides valuable insights into the factors influencing oocyte competence and utility rates in high responders undergoing IVF/ICSI. Physicians should be cautious when managing patients with a history of IVF/ICSI, endometriosis, or E2 decline during stimulation. For high responders, the dual suppression protocol and GnRH antagonist protocol are effective strategies for improving OUR and achieving favorable IVF outcomes. These findings underscore the importance of tailoring ovarian stimulation protocols to individual patient characteristics to optimize ART success.
doi.org/10.1097/CM9.0000000000001356
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