GnRH antagonists addition to gonadotropin-based COS protocols enhances treatment outcomes in patients with unexplained infertility

LH surges can be effectively inhibited by gonadotropin-releasing hormone (GnRH) agonists or antagonists. GnRH agonists should not be used during IUI cycles because of the length of time injections must be given before & during stimulation in order to fully downregulate GnRH receptors, the potential for excessive follicular stimulation, the increased cost, & patient annoyance. On the other hand, by competitively inhibiting GnRH receptors & inducing pituitary suppression, GnRH antagonists reduce the production of LH & follicle- stimulating hormone (FSH) within two to four hours. GnRH antagonists are well recognized for their ability to stop early LH surges.

This prospective research compared the outcomes of intrauterine insemination (IUI) & controlled ovarian stimulation (COS) in gonadotropin only versus gonadotropin & GnRH Antagonist cycles. GnRH antagonists demonstrated rapid suppression of LH and follicle-stimulating hormone (FSH) levels within 2–4 hours through competitive inhibition of GnRH receptors. This mechanism effectively prevented premature LH surges, reducing the risk of cycle disruption. In contrast, the use of GnRH agonists was not favored due to prolonged treatment duration, increased cost, risk of excessive follicular stimulation, and greater patient discomfort.

PGIMER was the site of the current investigation. To contrast the effects of gonadotropin alone against gonadotropin & GnRH antagonist during intrauterine insemination (IUI) & controlled ovarian stimulation (COS). A total of sixty couples—thirty in each group—had infertility that could not be explained. Sixteen couples in Group A & twenty-eight couples in Group B completed their therapy.

1. Fourteen patients from Group A & two individuals from Group B were unable to complete their third IUI cycle.

2. The mean (SD) age of the females in group A was 31.88 years, whereas that of group B was 30.36 years.

3. The mean (SD) duration of infertility was 5.88 years for group A & 5.71 years for group B.

4. Baseline serum FSH levels were 6.74 IU/L in Group A & 6.54 IU/L in Group B.

5. The mean baseline serum LH levels in Group B were 4.64 IU/L & 4.83 IU/L, respectively.

6. The mean baseline levels of estradiol were 21.33 pg/ml for Group A & 28.71 pg/ml for Group B.

7. Group B had 1.25 follicles larger than 18 mm, but Group A had 1.35; this difference was not statistically significant (p = 0.464).

8. The mean midcycle endometrial thickness was more than 8 mm in both groups. 9.45 mm in group A & 9.14 mm in group B (p=0.537).

9. A total of 1112.5 IU of gonadotropins were given to Group A & 1051.7 IU to Group B.

10. Group B's mean blood LH levels were 9.30, which was statistically significant (p=0.001) compared to Group A's 3.23.

11. The mean blood progesterone levels were 0.69 pg/ml in Group B & 0.24 pg/ml in Group A; this difference was not statistically significant (p=0.093). Group B did not receive a GnRH antagonist, which prevented premature luteinization, which explains the same clinical pregnancy rates between the two groups.

12. The clinical pregnancy rate per patient was 2/8 (25%) in group A & 3/14 (21.5%) in group B; the difference was not statistically significant (p=0.848).

13. 2/8 (25%) of patients in group A & 3/14 (21.5%) in group B were still pregnant; the difference was not statistically significant (p=0.848).

The addition of GnRH antagonist to gonadotropin-stimulated IUI cycles had no discernible effect on clinical pregnancy rates, pregnancy loss rates, continuing pregnancy rates, or multiple pregnancy rates.

Source: Suri et al. / Indian Journal of Obstetrics and Gynecology Research 2026;13(2):258–262