C. Bergeron

Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment

OBJECTIVEnTo analyze the effects of clomiphene citrate (CC) on cervical mucus (CM) and endometrial morphology independently of hormonal changes encountered when CC is administered for ovulation induction.nnnDESIGNnVolunteers whose ovarian functions were temporarily suppressed (n = 18) by a long-acting GnRH agonist and 6 women of similar age suffering from premature ovarian failure (POF) received E2 and P. Half of the women also received CC (50 mg/d, days 2 to 6).nnnSETTINGnTertiary University Institution, Hôpital A. Béclère.nnnPATIENTS, PARTICIPANTSnEighteen volunteers suffering from infertility not related to a uterine cause and 6 women of similar age suffering from POF.nnnMAIN OUTCOME MEASUREnPlasma gonadotropins, E2, and P were measured at baseline to confirm that the ovaries were inactive and twice weekly during physiological E2 and P replacement. Cervical mucus was analyzed on day 14 and scored from 0 to 15. Endometrial biopsies were obtained on replacement days 20 and 24 for conventional histology and immunocytochemistry analysis of estrogen receptors and progesterone receptors (PR). Premature ovarian failure women whose results have been previously published served as controls for day 20 biopsies.nnnRESULTSnCervical mucus scored lower in women who received CC (5.5 +/- 3.2) than in controls (13.6 +/- 4.7, mean +/- SEM). On day 20, endometrial findings were similar in women treated with CC and in controls. On day 24, specimens showed a significant delay in endometrial maturation in women treated with CC. On day 24, only staining for PR selectively persisted in endometrial stroma, and no difference was observed between women who received CC and controls.nnnCONCLUSIONnOur results indicate that CC significantly alters CM quality and late luteal phase endometrial morphology despite physiological levels of plasma E2 and P. Hence, clinicians should monitor E2 levels when using CC, and caution should be exerted when supraphysiological levels of E2 are not present to counterbalance the effects of CC on the CM and the endometrium.

7 Immunocytochemical localization of oestradiol and progesterone receptors in human endometrium: A tool to assess endometrial maturation

Uterine oestrogen (ER) and progesterone (PR) receptors are subject to fine hormonal control by oestradiol and progesterone. In order to assess the role of ER and PR measurement in the evaluation of endometrial maturation, both receptors were studied by immunocytochemical techniques using monoclonal antibodies during the menstrual cycle, and in women with inactive ovaries treated by different regimens of hormonal substitution with oestradiol and progesterone. During the normal menstrual cycle, the concentrations and distribution of ER and PR changed markedly. During the mid follicular period (days 7-8), a small proportion of stromal and glandular cells stained positively for PR while staining for ER was more intense and more frequent. During the late follicular phase and early luteal period (days 9-19), the staining for PR increased markedly in glandular cells. During the mid and late luteal phase (days 21-27), ER and PR staining disappeared in glandular cells. Thus, while oestradiol increases the staining for ER and PR in both glands and stroma, progesterone decreases ER and PR staining in the glands in a dramatic fashion. These variations, especially the disappearance of PR under the effect of progesterone, are potentially useful for studying the cumulative effect of progesterone on endometrial maturation. This was confirmed in anovulatory women, where a late luteal phase aspect was observed, i.e. the absence of a reduction in ER and PR in glandular cells. In women with ovarian failure, the disappearance of ER and PR in glandular cells is correlated with the duration of progesterone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled preparation of the endometrium with exogenous estradiol and progesterone in women having functioning ovaries

OBJECTIVEnTo determine if controlled preparation of the endometrium with exogenous estradiol (E2) and progesterone (P) could be achieved in women retaining their ovarian function without requiring prior ovarian suppression with a long-acting agonist of gonadotropin-releasing hormone (GnRH-a).nnnDESIGNnProspective feasibility study of a new simplified hormone regimen for preparation of endometrium receptivity. Six volunteer women received transdermal E2 and vaginal P without prior suppression of their ovarian function with GnRH-a. The control group consisted of previously reported cases receiving GnRH-a and E2 and P.nnnSETTINGnAcademic tertiary care institution.nnnPATIENTSnSix volunteer women.nnnMAIN OUTCOME MEASURESnParticipants received transdermal E2 and P after a regimen designed to duplicate the plasma E2 and P levels seen in the menstrual cycle.nnnINTERVENTIONnEndometrial biopsy.nnnRESULTSnPlasma luteinizing hormone increased to surge levels in one woman on day 11, in two on day 12, and on day 14 in the remaining three women. No follicular growth was noticed on ultrasound, and no increase in plasma P occurred before the onset of P administration on day 15. Day 20 endometrium specimens showed early secretory changes as previously reported in women deprived of ovarian function receiving similar hormonal treatment.nnnCONCLUSIONSnOur results indicate that controlled preparation of the endometrium can be achieved with exogenous E2 and P without prior ovarian suppression with a GnRH-a in women having functioning ovaries. Hence, administration of exogenous E2 and P appears to be a viable simpler alternative to the combined administration of GnRH-a and exogenous E2 and P, which avoids the side effects and the cost of GnRH-a.