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. 2025 Aug 21;14(16):5901.
doi: 10.3390/jcm14165901.

Optimizing Ovarian Stimulation for IVF in PCOS Patients: A Novel Day 1 GnRH Antagonist Protocol

Sudarsan Ghosh Dastidar  1 , Biswanath Ghosh Dastidar  1   2 , Ratna Chattopadhyay  3 , Chandan Chakraborty  4
Affiliations

Optimizing Ovarian Stimulation for IVF in PCOS Patients: A Novel Day 1 GnRH Antagonist Protocol

Sudarsan Ghosh Dastidar et al. J Clin Med. .

Abstract

Objectives: Gonadotropin-releasing hormone (GnRH) antagonist protocols are preferred in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization (IVF) as they provide the best combination of flexibility, acceptable outcomes, and safety. Numerous studies have compared outcomes between GnRH agonist long protocol and standard flexible antagonist protocol. However, there are scant studies investigating the effectiveness of antagonist administration from day 1 of ovarian stimulation in PCOS patients. Methods: We performed a retrospective cohort study to compare laboratory and clinical outcomes in IVF between standard flexible day 5/day 6 versus day 1 GnRH antagonist protocol in PCOS patients. Results: Our data indicates significantly superior oocyte yield and top-quality embryo proportion in patients with antagonists from day 1. Cumulative clinical pregnancy rates also tended to be superior in this group. Conclusions: Our findings indicate that administration of GnRH antagonists from day 1 of stimulation in PCOS patients undergoing IVF may lead to superior results.

Keywords: GnRH antagonist; in vitro fertilization (IVF) outcome; luteinizing hormone (LH); ovarian stimulation (OS); pituitary suppression; polycystic ovarian syndrome (PCOS).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic depiction of typical ovarian Stimulation protocols. In Group 1, GnRH Antagonist (Cetrorelix acetate 0.25 mg daily injections) was started from day 1 of stimulation concurrently with r-FSH (A); In Group 2, r-FSH was started on cycle day 1or 2 and flexible GnRH antagonist administration initiated from day 5 or 6 of stimulation (B).
Figure 2
Figure 2
Comparison of laboratory outcome measures between 2 groups. Box and whisker plots showing that (A) number of oocytes/COCs retrieved, (B) Number of oocytes fertilized to 2PN stage, (C) number of day 3 cleavage stage embryos formed, and (D) number of top quality day 3 embryos generated; were all greater (p < 0.05) in Group 1 (Day 1 Antagonist, depicted in Green) in comparison to Group 2 (Day 5/day 6 Antagonist, depicted in Orange).
Figure 3
Figure 3
Density distributions of laboratory outcome parameters compared between the 2 groups. Distribution plots showing (A) number of oocytes/COCs retrieved, (B) Number of oocytes fertilized/2PN Number, (C) number of day 3 embryos formed, and (D) number of top quality embryos formed; compared between Group 1 (Day 1 Antagonist, in Blue) and Group 2 (Day 5/day 6 Antagonist, in orange).
Figure 4
Figure 4
Comparison of pregnancy outcomes between Group 1 (Day 1 Antagonist) and Group 2 (Day 5/6 Antagonist). (A) Bar graph showing number of patients who became pregnant (blue) vs. number who did not get pregnant (orange), (B) Pie chart showing proportions of patients (Clinical pregnancy rate per stimulation cycle) who became pregnant (blue) vs those who did not (orange) in the 2 groups.
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