Poor ovarian response and the possible role of natural and modified natural cycles

About 20% of women undergoing in vitro fertilization struggle with poor ovarian response, indicating a poor prognosis related to low response following ovarian stimulation. Indeed, poor ovarian response, that is associated with both high cancelation rates and low live birth rates, still represents one of the most important therapeutic challenges in in vitro fertilization. In this context, natural cycle/modified natural cycle– in vitro fertilization, as a ‘milder’ approach, could be a reasonable alternative to high-dose/conventional ovarian stimulation in poor ovarian responders, with the aim to retrieve a single oocyte with better characteristics that may result in a single top-quality embryo, transferred to a more receptive endometrium. Moreover, modified natural cycle– in vitro fertilization may be cost-effective because of the reduced gonadotropin consumption. Several studies have been published during the last 20 years reporting conflicting results regarding the use of natural cycle/modified natural cycle– in vitro fertilization in women with poor ovarian response; however, while most of the studies concluded that mild stimulation regimens, including natural cycle/modified natural cycle– in vitro fertilization, have low, but acceptable success rates in this difficult group of patients, others did not replicate these findings. The aim of this narrative review is to appraise the current evidence regarding the use of natural cycle/modified natural cycle– in vitro fertilization in poor ovarian responders.

Clomiphene Citrate Priming Increases Sensitivity During Ovarian Stimulation in Poor Ovarian Responders Undergoing In Vitro Fertilization Treatment: A Retrospective Cohort Study

Background: Since ovarian stimulation was introduced as an assisted reproductive technology, poor ovarian response (POR) management has challenged clinicians. Guidance on optimally managing patients with poor response and/or low sensitivity to ovarian stimulation is still lacking. We aimed to investigate whether a clomiphene citrate (CC) priming protocol could increase ovarian sensitivity in poor ovarian responders. Methods: This single-center retrospective cohort study included 294 patients (374 ovarian stimulation cycles). Of these, 193 cycles were treated by a CC priming antagonist protocol (study group) and 181 by the classical flexible gonadotropin-releasing hormone antagonist protocol (control group). Stimulation data and laboratory and clinical outcomes were compared between the groups. Results: Total gonadotropin dosage and dosage per follicle were considerably lower, the follicle-to-oocyte index was significantly higher, and the gonadotropin duration was shorter in the study group. After adjusting for potential confounders, multivariate regression analysis showed that cumulative ongoing pregnancy remained comparable between the groups (adjusted odds ratio: 0.761, 95% confidence interval: 0.300-1.933, P = 0.566). Age, body mass index, gonadotropin dosage per follicle, and the follicle-to-oocyte index were directly associated with the reproductive outcomes. The result of the sensitivity analysis showed that patients stimulated by the CC priming antagonist protocol were administered less gonadotropin (1,739.09 ± 719.39 vs. 3,114.77 ± 1,171.23, P < 0.001) at a lower gonadotropin dosage per follicle (637.36 ± 373.05 vs. 1286.26 ± 976.66, P < 0.001) and for a shorter duration (6.58 ± 2.23 vs. 9.80 ± 1.90, P < 0.001). Conclusions: The CC priming antagonist protocol offered a convenient and patient-friendly way to increase ovarian sensitivity during ovarian stimulation in poor ovarian responders.

Development and Validation of a Clinical Pregnancy Failure Prediction Model for Poor Ovarian Responders During IVF/ICSI

BackgroundsDespite the great advances in assisted reproductive technology (ART), poor ovarian response (POR) is still one of the most challenging tasks in reproductive medicine. This predictive model we developed aims to predict the individual probability of clinical pregnancy failure for poor ovarian responders (PORs) under in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).MethodsThe nomogram was developed in 281 patients with POR according to the Bologna criteria from January 2016 to December 2019, with 179 in the training group and 102 in the validation group. Univariate and multivariate logistic regression analyses were used to identify characteristics that were associated with clinical pregnancy failure. The nomogram was constructed based on regression coefficients. Performance was evaluated using both calibration and discrimination.ResultsAge &gt;35 years, body mass index (BMI) &gt;24 kg/m2, basic follicle-stimulating hormone (FSH) &gt;10 mIU/ml, basic E2 &gt;60 pg/ml, type B or C of endometrium on human chorionic gonadotropin (hCG) day, and the number of high-quality embryos &lt;2 were associated with pregnancy failure of POR patients. The area under the receiver operating characteristic curve (AUC) of the training set is 0.786 (95% confidence interval (CI): 0.710–0.861), and AUC in the validation set is 0.748 (95% CI: 0.668–0.827), showing a satisfactory goodness of fit and discrimination ability in this nomogram.ConclusionOur nomogram can predict the probability of clinical pregnancy failure in PORs before embryo transfer in IVF/ICSI procedure, to help practitioners make appropriate clinical decisions and to help infertile couples manage their expectations.

P–657 Prostaglandin D2 is correlated with follicles development and a reliable marker of ovarian reserve of poor ovarian responder patients

Study question Is the prostaglandin D2 (PGD2) associated with growing follicles and ovarian reserve of poor ovarian responders? Summary answer PGD2 is correlated with ovarian stimulation activity and follicle growth. Especially, poor ovarian responders show a significant decrease in the level of follicular fluid. What is known already Prostaglandins (PGs) are involved in the female reproductive process, mainly ovulation, fertilization, and implantation. Study design, size, duration We investigated the PGD2 level in the follicular fluid of poor ovarian responders. The collection of human follicular fluid was approved by the Institutional Research and Ethical Committees of CHA University (approval number: 1044308–201611-BR–027–04) from January to December 2019. Follicular fluid was collected from patients with normal ovarian response and patients with POR. Participants/materials, setting, methods We studied whether prostaglandin has related to POR in the clinical key factor by measuring human follicular fluid. Follicular fluid was collected from patients with normal ovarian response and patients with POR. The concentration of PGD2 in follicular fluid was determined with ELISA kits following the manufacturer’s protocol. Main results and the role of chance We analyzed the level of PGD2 in the follicular fluid of patients with normal ovarian response and patients with POR using an ELISA. The PGD2 concentration was significantly lower in the follicular fluid of patients with POR than in the follicular fluid of young and old patients with normal ovarian response. Limitations, reasons for caution This study has an identification of biomarker of the clinical samples as POR criteria patients. Therefore, further investigations aimed at specific recovery of low PGD2 metabolic activity in the CCs during control ovarian stimulation. Wider implications of the findings: Until now there is no specific biomarker of POR. AMH is just an ovary reserve marker for an indication of ovary function. PGD2 is one of the metabolites in steroid metabolism in the ovary. Therefore, we can find some cure through further study for improved PGD2 production to POR patients. Trial registration number none