Endocrine changes in women conceiving during treatment with an LHRH agonist

Abstract

We report on eight patients who conceived during pituitary desensitization with buserelin in the luteal phase of the menstrual cycle. Pregnancy was diagnosed between day 12 and 21 of buserelin administration. Analysis of serum luteinizing hormone on day 12 showed that pituitary desensitization occurred in conjunction with increasing production of ovarian steroid hormones. Serum concentrations of human chorionic gonadotrophin (HCG) were less than 10 IU/l on day 1 of buserelin administration for seven of the eight patients. The serum concentration of HCG on day 12 showed a median value of 722 IU/l (range 14.6-798 IU/l). Five of the eight patients were given HCG support (10,000 IU) following the diagnosis of pregnancy--three of these patients have ongoing pregnancies and the remaining two had blighted ova on scan. Of the remaining three patients, one had a singleton pregnancy which miscarried at 9 weeks, one had a blighted ovum on scan and bled per vagina shortly after this, and one bled per vagina prior to a scan being carried out. Our results show that pregnancy can occur during pituitary desensitization with buserelin, despite patients being counselled not to have unprotected intercourse in the cycle during which administration commences. An HCG assay on day 1 of buserelin administration is not helpful. Pregnancy should be suspected when ovarian steroid production persists despite complete pituitary down-regulation.

Quantitative Gonadotropin-Releasing Hormone Gene Expression and Immunohistochemical Localization in Human Endometrium Throughout the Menstrual Cycle1

“…Encouraged by the evidence that large doses of GnRH or GnRH-a were able to induce abortion or delay implantation in rats and baboon monkeys [7,59], one of the first clinical GnRH-a experiments in humans was to assess a possible postcoital and postimplantation contraceptive effect. The surprising outcomes of those studies was that high doses of super-reactive GnRH-a not only failed to block implantation or induce abortion in humans [60] but rather seemed to enhance implantation [24][25][26][27][28][29][30][31][32][33][34][35][36]. The exact mechanism by which GnRH-a favors pregnancy during the periimplantation period has remained unknown until present.…”

“…The inadvertent exposure of human pregnancy during the early stages of embryonic implantation to GnRH-a has been reported in IVF patients, and the clinical experience in those cases has suggested not only that undesired effects are unlikely but that the analogue might enhance implantation [24][25][26][27][28][29][30][31][32][33][34][35][36]. Moreover, it has been reported that patients with long history of infertility and unsuccessful treatment by different modalities have conceived repeatedly under the administration of GnRH-a [26,37], with the suggestion that these conceptions may have been favored by the analogue.…”

Serum Inhibin as an Index of Ovarian Function in Women Undergoing Pituitary Suppression and Ovarian Stimulation in an in vitro Fertilization Program

“…An additional complication of com mencing treatment in the luteal phase is that pregnancy can arise if the couple have unprotected intercourse in that cycle [7], and this must be identified to minimize GnRH-a administration during the early stage of preg nancy. Once exogenous gonadotropins are given to stim ulate follicular growth, then monitoring is required to observe the ovarian response [8] and to time the admin istration of the ovulatory trigger for the collection of mature oocytes [9], Endocrine assessments are important in monitoring ovarian function and, coupled with ultrasonography, give accurate information during pituitary suppression with GnRH-a [4] and ovarian stimulation with exoge nous gonadotropins [10], Also, the introduction of new approaches to augment the ovarian response to exoge nous gonadotropins, for example the treatment of poor responders by and growth hormone [12], has increased the need for reliable monitoring systems.…”

Multiple gestation following gonadotrophin releasing hormone therapy for the treatment of minimal endometriosis

“…This unfortunate complication clearly emphasises the importance of establishing the date of the last menstrual period before commencing GnRHa treatment and underlines the need for contraception if treatment is commenced in the follicular phase. Finally, with reports of pregnancies occurring with luteal phase administration (Martinez et al 1988; Ishenvood et al 1990) as with danazol for the treatment of endometriosis, we should ensure that nonhormonal methods of contraception are advised throughout treatment, no matter where in the menstrual cycle the initial dose of GnRHa is given.…”