Cycle pattern and pregnancy rate following combined clomiphene-estrogen therapy

Pathophysiology of polycystic ovarian disease: new insights

Insler V et al., 1991 · Hum Reprod

The incidence of polycystic ovarian disease (PCOD) varies from 0.6 to 92%, depending on the parameters analysed, PCOD has been reported to appear in association with Cushing's Syndrome, adrenal hyperplasia, hypothyroidism, adrenal and ovarian tumours and some genetic abnormalities. The controversy regarding the pathophysiological mechanism underlying the disease still persists. Critical evaluation of old data, assessment of new findings concerning the possible role of insulin, growth factors and their binding proteins, and extrapolation of neuroendocrinological experiments enabled the construction of a concise hypothesis of the pathophysiology of PCOD. According to this hypothesis, PCOD is a multifactorial disease. The sequence of events finally leading to clinical manifestation of the disease (hyperandrogenism, abnormal luteinizing hormone pulsatility pattern and ovulation disturbances) may originate in different organs or be triggered by different mechanisms. It may stem from the adrenals, the hypothalamus or higher central nervous system centres, or from the ovary itself; it may originate from excess of fat tissue usually combined with hyperinsulinism; or may be the result of a net increase in active growth factors. Each of the above disturbances probably appears early in life, much before the clinical signs of the disease are evident. Predisposing factors such as gestational diabetes of the mother, childhood obesity, borderline adrenal hyperplasia and late menarche have to be looked for as early as possible in order to prevent the late consequences of the disease, such as increased risk of infertility, endometrial and breast cancer and cardiovascular disease.

Sperm storage in the human cervix: a quantitative study

Insler V et al., 1980 · Fertil Steril

Twenty-five women scheduled for hysterectomy for nonmalignant disease participated in the study. Sperm storage in endocervical crypts was examined in three groups of nine women pretreated with estrogen and inseminated with normal semen, nine women pretreated with gestagen and inseminated with normal semen, and seven women pretreated with estrogen and inseminated with abnormal semen. The number of crypts containing spermatozoa (colonized crypts) and the sperm density per crypt were examined in serially sectioned cervices. In estrogen-pretreated cervices both the percentage of colonized crypts and the sperm density were significantly higher than in gestagen-pretreated cervices. Large and giant crypts proved to be the main storage facility for spermatozoa. The localization of crypts along the endocervical canal did not influence sperm storage. The quality of semen appeared to be of critical importance to sperm storage. The percentage of colonized crypts and sperm density were severly reduced in patients inseminated with abnormal semen.

The Cervical Score: A Simple Semiquantative Method for Monitoring of the Menstrual Cycle

Insler V et al., 1972 · Intl J Gynecology & Obste

Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after clomiphene therapy

Hack M et al., 1972 · JAMA

Eighty-six women reached at least 20 weeks' pregnancy in 96 instances, after ovulation induced by clomiphene citrate. Although 37 of the women had 44 previous pregnancies, there had been a high pregnancy wastage (70.5%) producing only 13 live infants prior to the successful clomiphene therapy. After clomiphene therapy, pregnancies were normal except for a high incidence of toxemia (16.7%) and a possibly increased incidence of prediabetes. The pregnancies resulted in 88 single and 8 twin births. The total fetal and neonatal loss was 6.7%. The loss of single births (3.1%) included two stillbirth infants of prediabetic mothers. The twin loss of 25% was due to prematurity. The incidence of congenital malformations was within normal limits.

Further clinical experience with clomiphene citrate

Macgregor AH et al., 1968 · Fertil Steril

FURTHER OBSERVATIONS ON THE EFFECTS OF CLOMIPHENE CITRATE IN ANOVULATORY FEMALES

Kistner RW, 1965 · Am J Obstet Gynecol

INDUCTION OF OVULATION WITH CLOMIPHENE CITRATE

Naville AH et al., 1964 · Fertil Steril

Outcome of pregnancy after clomiphene therapy

Ahlgren M et al., 1976 · Acta Obstet Gynecol Scand

Of 159 pregnancies conceived after clomiphene therapy, 141 ended in childbirth, including seven sets of twins. There was a probable increase in the number of infants born with major malformations. These were exclusively to women who had not previously borne a normal infant. The incidence of malformed infants compares well with that published after gonadotropin therapy. The possibly higher incidence of malformations seen after drug-induced ovulation would therefore seem to be due to the underlying subfertility state and thus not a direct drug effect.