Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada
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Abstract |
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Key words: clomiphene/follicle/pregnancy/superfetation
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Introduction |
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Case report |
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In the first cycle, a single dominant follicle of 20 mm was seen on day 13. Ovulation was triggered with human chorionic gonadotrophin (HCG) (Profasi; Serono Canada Inc., Oakville, Ontario, Canada; 10 000 IU s.c.). Intrauterine insemination was performed 24 and 48 h later. On day 26 of the cycle, the patient reported that her menstruation resumed. Transvaginal ultrasonography 4 days later revealed the absence of any ovarian cyst, and an endometrial thickness of 3.4 mm. The same regime of clomiphene treatment was administered. On day 14 of this cycle, transvaginal ultrasonography revealed three follicles of 13, 16 and 18 mm. The endometrial thickness was 6.1 mm. Ovulation was triggered with HCG, and insemination was performed as in the preceding cycle. On day 28 of the cycle, the patient presented with a 10-day period of vaginal spotting and mild low abdominal pain. A blood sample was withdrawn for ß-HCG measurement, and the concentration was found to be 16 652 IU/ml. Subsequent transvaginal ultrasonography revealed a right tubal ectopic pregnancy with fetal cardiac activity compatible with 7 weeks gestation. The patient was then treated with laparoscopic salpingostomy. The operation and the postoperative recovery were uneventful.
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Discussion |
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In early pregnancy, small and undeveloped follicles populate the ovaries (Govan, 1968). After 810 weeks gestation, follicular growth and atresia continue until term. The oocytes per se, however, are functionally intact. It has been demonstrated (Hwang et al., 1997
) that immature oocytes retrieved from the ovary at the time of delivery can be fertilized and initiate a pregnancy.
The ovulatory quiescence is due to an inhibition of the pituitary during pregnancy, and this has been demonstrated by a decreased FSH and LH response to gonadotrophin-releasing hormone (GnRH) administration (Rubenstein et al., 1978). The suppression of gonadotrophin is likely due to the high concentration of oestradiol, progesterone and possibly inhibin in pregnancy. Exogenous gonadotrophin can overcome this inhibition however, leading to follicular growth.
Unlike gonadotrophin, which has a direct effect on the ovary, the primary site of action of clomiphene citrate is the hypothalamus (Kerin et al., 1985). In animal models, clomiphene also exerts an effect on the pituitary and directly stimulates gonadotrophin release, independent of its action on GnRH (Adashi, 1986
). In the current patient, clomiphene induced follicular development and maturation in pregnancy, which suggests thatat least in ectopic pregnancyclomiphene can reverse pregnancy-induced pituitary insensitivity. It is possible that pituitary suppression in women with abnormally implanted pregnancy is incomplete. A possible case of superfetation related to clomiphene citrate was previously published (Bsat and Seoud, 1987
); however follicular development was not demonstrated, and the possibility of symmetrical intrauterine growth restriction could not be discounted.
It is concluded that clomiphene citrate can induce follicular growth and maturation in pregnancy, perhaps by reversing the pregnancy-induced pituitary suppression.
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Notes |
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References |
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Submitted on December 8, 2000; accepted on March 7, 2001.