Abstract

Background: Prior studies have shown that patients with a >10% estradiol (E2) rise after trigger had more oocytes retrieved than plateauing or decreasing E2 responders. However, multiple follicles develop at different stages of maturation during controlled ovarian stimulation (COS) and may exhibit different responses to trigger. The association between the magnitude of E2 increase and oocyte retrieval outcomes is still unclear.Methods: This was a retrospective cohort study of 2,898 women undergoing their first COS cycles with normal response from January 2014 to December 2017 at a tertiary-care academic medical center. Patients were categorized into five groups according to the percentage increase in E2 levels before and after dual trigger: <10.0%, 10.0–19.9%, 20.0–29.9%, 30.0–39.9%, and ≥40.0%. Univariable and multivariable linear regression analysis were performed to explore the association between E2 increase and oocyte/mature oocyte yield, while logistic regression was used to assess its effect on low oocyte/mature oocyte yield (<10th percentile).Results: The post-trigger E2 increase was negatively associated with both oocyte yield (P-trend < 0.001, adjusted P-trend = 0.033) and mature oocyte yield (P-trend < 0.001, adjusted P-trend = 0.002). Compared with a <10.0% E2 increase after trigger, patients with a ≥40.0% rise had fewer mature oocyte yield [adjusted mean absolute difference [MD] = −5.2, 95% confidence interval [CI]: −8.2–−1.8] and higher risk of low mature oocyte yield (adjusted odds ratio [OR] = 1.64, 95% CI: 1.04–2.60), whereas no statistical significance was found in oocyte yield (adjusted MD = −2.7, 95% CI: −6.1–0.8) and low oocyte yield (adjusted OR = 1.48, 95% CI: 0.96–2.28). In addition, the rates of implantation, positive pregnancy test, clinical pregnancy, ongoing pregnancy, pregnancy loss, and live birth were comparable among the 1,942 frozen embryo transfer cycles with embryos originating from different groups of E2 increase (all P > 0.05).Conclusions: A higher E2 rise after dual trigger is independently associated with a lower oocyte and mature oocyte yield in normal responders. Further studies are needed to explore the efficacy of individualized time interval from trigger to oocyte retrieval based on the magnitude of E2 increase after trigger.

Highlights

  • In vitro fertilization (IVF) treatment stimulates many of the physiological processes occurring in the natural menstrual cycle in a supraphysiological manner

  • To rescue the defective luteal phase function and subsequently comprised pregnancy outcomes caused by the gonadotropin-releasing hormone agonist (GnRHa)-induced luteolysis [6], the new concept of dual trigger has been introduced that combines a single bolus of GnRHa with a small dose of Human chorionic gonadotropin (hCG) [7, 8]

  • A total of 7,996 patients were selected from our database who received progestin-primed ovarian stimulation (PPOS) protocol for ovarian stimulation and dual trigger for final oocyte maturation during their first IVF/intracytoplasmic sperm injection (ICSI) cycles

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Summary

Introduction

In vitro fertilization (IVF) treatment stimulates many of the physiological processes occurring in the natural menstrual cycle in a supraphysiological manner. The mode by which oocyte maturation is induced has significant impact on the efficacy of oocyte retrieval, the chance of pregnancy, and the safety of IVF treatment [2]. Human chorionic gonadotropin (hCG), as the most commonly used agent to trigger final oocyte maturation, shares structural similarity, and activates the same receptor as LH [3]. Owing to the prolonged half-life and the sustained luteotropic activity of hCG [4], the risk of ovarian hyperstimulation syndrome (OHSS) is increased in patients hyperresponsive to ovarian stimulation. As an alternative to hCG, gonadotropin-releasing hormone agonist (GnRHa) elicits an endogenous surge of LH and follicular stimulating hormone (FSH) by acting at the GnRH receptors in the pituitary gland, leading to the reduction of OHSS incidence, and the retrieval of more MII oocytes [5, 6]. The association between the magnitude of E2 increase and oocyte retrieval outcomes is still unclear

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