FURTHER OBSERVATIONS ON THE EFFECTS OF CLOMIPHENE CITRATE IN ANOVULATORY FEMALES

Sequential use of clomiphene citrate and human menopausal gonadotropin in ovulation induction

Kistner RW, 1976 · Fertil Steril

In an effort to diminish the incidence of multiple pregnancy, ovarian hyper-stimulation syndrome, and the excessive cost of human menopausal gonadotropin (HMG) administration, a sequence of Clomid-HMG-human chorionic gonadotropin (HCG) was used in 80 patients with infertility due to prolonged amenorrhea. Criteria for this therapeutic regimen were: (1) normal seminal fluid analysis and postcoital test; (2) lack of withdrawal bleeding from progesterone following amenorrhea of more than 6 months' duration; (3) normal x-ray of the sella turcica and visual fields; (4) low serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels; (5) normal endoscopic examination; and (6) lack of response to clomiphene in excessive dose (200 mg daily for 5 days) or prolonged dose (100 mg daily for 10 days) with or without HCG, or apparent ovulatory response to the above sequence for five or six consecutive cycles without pregnancy. Clomiphene was administered in a dose of 100 mg daily for 7 days. HMG was then given in the following manner: two ampules daily for 4 days, then one ampule daily for 2 days (75 IU of FSH and 75 IU of LH/ampule). After a 24-hour interval without treatment, 10,000 IU of HCG were given and 2000 IU of HCG 4 days later. Twenty-three pregnancies occurred in 80 patients. However, 15 of the first 25 patients became pregnant--in these patients the only abnormality noted was lack of ovulation. Six additional pregnancies occurred subsequent to one or more unsuccessful cycles. Multiple pregnancies occurred in only two patients (twins delivered at 32 weeks in one and an abortion of five fetuses at 20 weeks in another). However, multiple pregnancy did not occur in any patient whose urinary estrogen level was monitored and in whom the level was 100 mug or less when the HCG was given. The ovarian hyperstimulation syndrome did not occur in any patient.

INDUCTION OF OVULATION WITH CLOMIPHENE CITRATE

Naville AH et al., 1964 · Fertil Steril

Action of MER-25 and of clomiphene on the human ovary

Smith OW et al., 1963 · JAMA

IT APPEARS TO BE WELL ESTABLISHED that the synthetic nonsteroidal analogue of chlorotrianisene (Tace), which has been given the generic name of clomiphene citrate (MRL/41)*, is capable of stimulating ovarian secretory activity in women.1-4 Perhaps the most convincing evidence for this is found in the high incidence of cystic ovaries observed among treated patients, together with the associated microscopic ovarian and endometrial changes, indicating that the cystic structures produced are functional.2,3 The striking similarity between the histopathology of this response to clomiphene and the ovarian response to administered gonadotropins of both human and animal origin has been pointed out by Southam and Janovski.2 With both forms of treatment, the degree of ovarian response to a given dosage appears to be unpredictable and all patterns of atypical stimulation have been observed. In view of this analogy, it has been logical to assume that the ovarian response

Further clinical experience with clomiphene citrate

Macgregor AH et al., 1968 · Fertil Steril

Clomiphene citrate: Its uses and observations on its probable action

Whitelaw MJ et al., 1964 · Am J Obstet Gynecol

Use of clomiphene citrate in women

Practice Committee of the American Society for Reproductive Medicine, 2003 · Fertil Steril

CLOMIPHENE CITRATE: FURTHER OBSERVATIONS ON ITS USE IN INDUCTION OF OVULATION IN THE HUMAN AND ON ITS MODE OF ACTION

Roy S et al., 1963 · Fertil Steril

Induction of ovulation in the human has been of considerable research interest for several decades. Various hormonal regimens and other procedures have been tried in the past.1 • 2 In spite of all these trials, the problem of ovulatory failure remains a frustrating dilemma for the physician. Recently, the induction of ovulation with clomiphene citrate in about 70% of anovulatory women was reported by our group.3- 6 It was felt that an important breakthrough in this difficult field of endeavor was at hand. 7- 9 Our observations have been confirmed by other groups of investigators.10- 12 The present report embodies a detailed analysis of the results of administration of this agent to 200 women, of whom 179 were anovulatory. The results of our studies on the probable mode of action of this drug are also discussed.