Suggestion and comment for CC preventing LH surge

30 03 2011

To the Editor:

I read with interest the article by Al-Inany et al. (1) in which the authors demonstrated the beneficial effects of the addition of clomiphene citrate (CC) to human menopausal gonadotropin (hMG) during intrauterine insemination (IUI) cycles to prevent a premature luteinizing hormone (LH) surge. Their study was well designed. Surprisingly, the endometrial thickness of both groups w thin, with an average thickness of less than 6.0 mm, which may reduce pregnancy rates as the authors mentioned.

This may be associated with the time of hCG injection, in my personal and institutional experience. In addition to clinical evidence, an observational study about follicle size on the day of hCG injection at our center found that endometrium would continue growing until the diameter of the follicle reached 24 mm and could get good embryos in IVF cycles. Therefore, we suggest delaying the administration of hCG even if the leading follicle exceeds 18 mm when the endometrial thickness is less than 6.0 mm.

On the other hand, serum estradiol (E2) levels increase with the growing follicles, which will result in the more frequent occurrence of premature LH surge in IUI cycles with ovarian stimulation. This may contribute to the observed efficacy of CC preventing LH surge.

Xin Chen, M.D., M.Sc.
Center for Reproductive Medicine
Department of Obstetrics and Gynecology
Nanfang Hospital
Southern Medical University,
Guangzhou, People’s Republic of China

Reference
1. Al-Inany H, Azab H, El-Khayat W et al. The effectiveness of clomiphene citrate in LH surge suppression in women undergoing IUI: a randomized controlled trial. Fertil Steril 2010;94:2167-71.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2011.03.098

The Authors Respond:

We would like to thank Dr. Chen for the interest in our work. (1)The comments raised in his letter to editor are highly valid. We agree that delaying hCG administration may allow endometrial thickness to increase but on the other hand, it will cause more and more premature LH surge (Ganerlix dose finding study).

The follicle diameter of 18 mm as a cutoff value for triggering of ovulation is well agreed upon by many investigators all over the world, and the bilayered endometrial thickness (BET) of 5 mm or more has been used by many authors as an acceptable cutoff value for achieving pregnancy in IVF-ET cycles. Accordingly, in the present study, the endometrial thickness cannot be considered suboptimal for implantation, keeping in mind that implantation will take place seven days after hCG administration: 36-40 hours for ovulation to occur and five days for implantation to happen. These seven days would allow for endometrial growth to continue. In addition , delaying hCG will cause more elevation of E2 level, as the author mentioned, and this relatively high level of E2 could have negative impact on chance of conception(3).

Hesham Al-Inany, M.D., Ph.D.
Cairo University
Cairo, Egypt

References
1. Al-Inany H, Azab H, El-Khayat W et al. The effectiveness of clomiphene citrate in LH surge suppression in women undergoing IUI: a randomized controlled trial. Fertil Steril 2010;94:2167-71.

2. Leibovitz Z, Grinin V, Rabia R, Degani S, Shapiro I, Tal J, Eibschitz I, Harari O, Paltieli Y, Aharoni A, Zeevi J, Ohel G. Assessment of endometrial receptivity for gestation in patients undergoing in vitro fertilization, using endometrial thickness and the endometrium-myometrium relative echogenicity coefficient. Ultrasound Obstet Gynecol. 1999 Sep;14(3):194-9.

3. Orvieto R, Zohav E, Scharf S, Rabinson J, Meltcer S, Anteby EY, Homburg R. The influence of estradiol/follicle and estradiol/oocyte ratios on the outcome of controlled ovarian stimulation for in vitro fertilization. Gynecol Endocrinol. 2007 Feb;23(2):72-5.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2011.03.099

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