Hack, M., Brish, M., Serr, D. M., Insler, V., Salomy, M., & Lunenfeld, B. (1972). Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after clomiphene therapy. JAMA, 220(10), 1329-1333.
Hack M, Brish M, Serr DM, Insler V, Salomy M, Lunenfeld B. Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after clomiphene therapy. JAMA. 1972;220(10):1329-1333.
Hack, M., et al. "Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after clomiphene therapy." JAMA, vol. 220, no. 10, 1972, pp. 1329-1333.
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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.
Among 2,496 infertile Israeli women treated between 1964 and 1974, 143 cancer cases were observed as compared with 116.1 expected (standardized incidence ratio (SIR) = 1.2, 95% confidence interval (CI) 1.0-1.5) through 1991. Site-specific analysis revealed 12 ovarian cancers versus 7.2 expected (SIR = 1.6, 95% CI 0.8-2.9), 21 endometrial cancers versus 4.3 expected (SIR = 4.85, 95% CI 3.0-7.4), and 59 breast cancers versus 46.6 expected (SIR = 1.3, 95% CI 0.96-1.6). Sensitivity analysis revealed that confounding was unlikely to explain the raised risk of endometrial cancer, but nulliparity might explain the increased risk of ovarian cancer. The excess of endometrial cancer was prominent among patients with normal estrogen production but progesterone deficiency (SIR = 9.4, 95% CI 5.0-16.0). The risk for ovarian cancer was similar among the total groups of treated and untreated patients (SIR = 1.7 vs. 1.6). The standardized incidence ratio for endometrial cancer was higher among the treated group than the untreated group, although not significantly. Treatment with ovulation-inducing drugs does not appear to increase the risk for ovarian cancer, but its role cannot be completely excluded.
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.
A prospective study of six unselected couples diagnosed as having unexplained infertility was done. In three of six patients, subtle abnormalities in follicular development were detected. In the first case poor follicular growth was observed. There was a premature small rise of luteinizing hormone (LH) with subsequent low levels of estradiol (E2) in the late follicular phase and unusual wide LH peak. This was followed by low progesterone levels in the luteal phase. In the second case follicular growth was abrupted by premature LH surge. This surge was triggered by early rise of E2 level while the follicle was still small in size. In the third case luteinized unruptured follicle syndrome was diagnosed, on ultrasound examination. All of the abnormalities were repetitive.
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 outcome of pregnancy was studied in all women conceiving after ovulation induction with clomiphene at the gynaecological endocrine clinics operating in 2 Tasmanian cities. In 156 pregnancies where details were available, the main findings were: abortion rate 10.3%; multiple pregnancy rate 4.1%; congenital abnormality rate 3.6%; and perinatal mortality rate 3.5%. The results are compared with other reported series.
Pregnancy following a period of infertility was considered to be an increased risk for the fetus. During a period of 3 years (1983-85), 748 couples were seen at this infertility clinic; 515 women (68.9%) conceived, and were followed up and studied prospectively. Fifteen of these women moved out of the area. We analysed the results of pregnancies for the remaining 500, (Group 1) and compared them with the outcome for the total obstetric population (Group 2) during the same period. Mean age at conception in the infertility group (Group 1) was 31.8 (+/- 2.7, 2 SD) years, as compared with 23.7 (+/- 2.9, 2 SD) in the total hospital obstetric population (Group 2) (p less than 0.05). The incidences of spontaneous abortion for the two groups (8 and 6.2%) did not differ (p greater than 0.05). However, the incidence of ectopic pregnancy was higher (3.0%) in Group 1 than in Group 2 (1.5%) (p less than 0.01). The incidence of pre-existing hypertensive vascular disease (7.7%) complicating pregnancy and multiple pregnancy (4.1%) was significantly higher in Group 1 than in Group 2 (1.5% and 1.4% respectively), (p less than 0.01). The incidences of induction of labor (29.5%) and elective operative delivery (10.6%) were higher in Group 1 (p less than 0.01). The incidences of infants with birth weight below the tenth centile (12.9%), of fetal distress in labor (14.6%) and a low Apgar score (0-5) (9.5%), were higher in Group 1, but there was no difference in the perinatal mortality rate between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
The experience of the gynecologic endocrinology and infertility clinic at The Johns Hopkins Hospital has been subjected to a nonconcurrent prospective analysis in an attempt to evaluate the gestational fate of clomiphene-related conceptions (study series, n = 86). This latter series was contrasted with a series of pregnancies following bilateral ovarian wedge resection (BOWR) (n = 51) in a comparative analysis of gestational outcome event rates. Post-therapy follow-up was available for varying time spans of up to 15 years. A 12.8% twinning rate constituted the single most important complication of clomiphene therapy, resulting in measurable increments in perinatal morbidity and mortality rates. The observation of a 26.5% spontaneous abortion rate would seem to suggest that clomiphene-related conceptions are at little or more risk for spontaneous abortion than would have been expected from the infertile population under discussion. A 3.1% incidence of post-clomiphene birth defects was not increased as compared with commonly quoted rates for the population at large. The corresponding incidence rates of twinning, spontaneous abortion, and birth defects for the BOWR series were 0%, 21.6%, and 0%, respectively.
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.
Hack, M., Brish, M., Serr, D. M., Insler, V., Salomy, M., & Lunenfeld, B. (1972). Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after clomiphene therapy. JAMA, 220(10), 1329-1333.
Hack M, Brish M, Serr DM, Insler V, Salomy M, Lunenfeld B. Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after clomiphene therapy. JAMA. 1972;220(10):1329-1333.
Hack, M., et al. "Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after clomiphene therapy." JAMA, vol. 220, no. 10, 1972, pp. 1329-1333.
