Ray V. Haning

Plasma estradiol is superior to ultrasound and urinary estriol glucuronide as a predictor of ovarian hyperstimulation during induction of ovulation with menotropins

In order to compare the effectiveness of 8:00 A.M. plasma 17 beta-estradiol (E2), 24-hour urinary estriol glucuronide (E3G), and ultrasound as predictors of ovarian hyperstimulation, 70 cycles of induction of ovulation with 5:00 P.M. to 8:00 P.M. injection of menotropins from 28 subjects were evaluated. Hyperstimulation was four times more frequent in pregnancy than in nonpregnancy cycles (P less than 0.005). The hyperstimulation score (range, 0 to 6) was correlated with plasma E2 (0.63, P less than 0.01), the number of follicles (0.31, P less than 0.05), the duration of treatment (0.31, P less than 0.05), and urinary E3G (0.25, P less than 0.05). Plasma E2 was the best predictor of the hyperstimulation score, and plasma E2 was far superior to both urinary E3G and the number of follicles. Management with ultrasound alone is insufficient to prevent severe ovarian hyperstimulation. With this protocol, human chorionic gonadotropin may be given as soon as the first follicle reaches 1.4 cm in diameter as long as plasma E2 is less than 4000 pg/ml. The values of plasma E2 are dependent on the interval between blood sampling and injection of menotropins.

Artificial donor insemination: fresh versus frozen semen; the patient as her own control

The efficacies of fresh versus cryopreserved semen in the treatment of male factor infertility by artificial insemination by donor (AID) semen were directly compared by using the patient as her own control. In any one cycle, either fresh or frozen semen was used. The type of semen preparation was randomly assigned for the first cycle and varied thereafter according to donor availability. The same donor was used for a given patient in six consecutive cycles. We treated 381 patients in this way. In 676 cycles fresh semen was used and 128 pregnancies were achieved. Fecundability, the chance of getting pregnant per cycle of exposure, was 18.9% with fresh semen. In 1200 cycles cryopreserved semen was used and 60 pregnancies occurred, for a fecundability of 5.0%. Therefore, in our clinic, fresh semen is more than three times as likely to induce pregnancy as frozen semen. The design that has been used in this therapeutic protocol provides a technique for internal quality control of the cryopreservation process and for the investigation of other variables potentially affecting the success rates with AID.

Ultrasound evaluation of estrogen monitoring for induction of ovulation with menotropins

Twenty-five cycles of induced ovulation with menotropins were investigated blindly with ultrasound to evaluate estrogen monitoring. Plasma 17 beta-estradiol (E2) and urinary estriol glucuronide (E3G) correlated with total ovarian volume (0.58, 0.58), total follicular volume (0.56, 0.52), volume of the largest follicle (0.53, 0.54), and days of administration of menotropins (0.49, 0.44), respectively. The mutual correlations of days of menotropin administration, volume of the largest follicle, E2, and E3G with total follicular volume explained the correlations of E2 and E3G with days of administration of menotropins and with volume of the largest follicle. Thus, multiple small follicles can reproduce the E2 or E3G levels associated with a single mature follicle if they result in the same total follicular volume. As menotropins were administered for progressively longer periods, the number of maturing follicles increased. We conclude that ultrasound appears to be useful for monitoring induction of ovulation with menotropins since it provides more accurate information on follicular number and size than can be obtained by estrogen determinations alone.

A Syndrome of Chronic Renal Failure and XY Gonadal Dysgenesis in Young Phenotypic Females Without Genital Ambiguity

A case of XY gonadal dysgenesis with renal failure is presented. Diagnosis was delayed four years post renal transplantation. A uterus, fallopian tubes, and vagina were present with a combined gonadoblastoma and dysgerminoma found in the right streak gonad. Six other similar cases have been reported, including concordance in a pair of monozygous twins. Because of the risk of gonadal malignancy, the serum FSH concentration should be determined in phenotypic females with primary amenorrhea and chronic renal disease. Due to a physiologic reduction in the serum FSH concentration in agonadal individuals between 5 and 11 years of age, a karyotype may be required to detect affected individuals during this interval. Gonadectomy should be performed in all cases of XY gonadal dysgenesis. A urinalysis and serum creatinine concentration should be obtained in girls presenting with XY gonadal dysgenesis. The serum FSH concentration and karyotype should be determined in females presenting with congenital nephrotic syndrome.

Diagnosis-specific serum 17β-estradiol (E2) upper limits for treatment with menotropins using a 125I direct E2 assay

Statistical evaluation of 133 cycles of induction of ovulation using generalized linear models demonstrated that the occurrence and severity of ovarian hyperstimulation was influenced by the serum 17 beta-estradiol (E2) concentration (P less than 0.001), conception (P less than 0.001), and the endocrinologic diagnosis, polycystic ovary syndrome (PCO) or hypothalamic amenorrhea (HA) (P less than 0.01). When menotropins were administered between 5:00 P.M. and 8:00 P.M. and blood was drawn at 8:00 A.M., an upper limit for serum E2 in patients with HA of 2417 pg/ml or an upper limit for patients with PCO of 3778 pg/ml gave an approximate 5% risk of severe ovarian hyperstimulation in conception cycles and a 1.3% risk of severe hyperstimulation in nonconception cycles. Comparison of our E2 radioimmunoassay involving extraction and chromatography to the Pantex immunodirect Estradiol 125I kit (Pantex, Santa Monica, CA) demonstrated no detectable systematic error, allowing the use of these limits with either assay. The ovulating injection of human chorionic gonadotropin was given at 5:00 P.M. to 8:00 P.M. on the evening of blood drawing as soon as the first follicle reached an average diameter of 14 mm or greater. The ultrasound parameters allow the chance of pregnancy to be optimized and the chance of multiple gestation to be minimized. Serum E2 monitoring indicates when the risk of ovarian hyperstimulation is too great for human chorionic gonadotropin to be given.

Testosterone free index correlates best with dehydroepiandrosterone sulfate

Correlation coefficients for dehydroepiandrosterone sulfate (DHEAS) were determined in women on menotropin. DHEAS was significantly correlated with testosterone free index (TFI), 0.78**; percentage free testosterone (%FT), 0.66**; androstenedione (delta 4A), 0.66*; luteinizing hormone (LH), 0.55**; LH/follicle-stimulating hormone (FSH) ratio, 0.55**; 17-OH-progesterone (17-P), 0.55**; testosterone (T), 0.53**; weight (WT), 0.40**, urinary estriol glucuronide (E3G), 0.33*; and free cortisol index (FFI), 0.32*, with 43 df but not with prolactin (PRL), 0.25. Normal male DHEAS (3.5 +/- 1.2, 25) (microgram/ml; mean +/- standard deviation, n) was higher than normal female DHEAS (2.4 +/- 1.1, 27), P less than 0.01 and DHEAS in women on oral contraceptives (1.9 +/- 1.1, 17) was slightly lower than in normal females, P greater than 0.2. In the combined population (male, female, and females on oral contraceptives) DHEAS was correlated with TFI (0.56**), T (0.54**), %FT (0.52**), delta 4A (0.40**), and age (-0.40**) with 66 df and 17-P (0.30*) with 54 df. TFI appears to be one determinant of plasma DHEAS, **P less than 0.01. *P less than 0.05.

Laparoscopic Findings in Twenty-Five Failures of Artificial Insemination

The laparoscopic findings, treatment, and follow-up of 25 patients who failed artificial insemination donor (AID) were retrospectively evaluated. A high incidence (72%) of abnormal pelvic findings was encountered. Endometriosis was found in 60% and pelvic adhesions in 12% of the patients. The incidence of these two entities was not significantly different from their incidence in patients with unexplained infertility in the same institution (44% for endometriosis and 36% for adhesions). After surgical or medical treatment, a pregnancy rate of 22.2% (16.6% for endometriosis and 66.6% for pelvic adhesions) was achieved in patients with positive pelvic findings; in the group with negative pelvic findings, a pregnancy rate of 20% was achieved. The value of diagnostic laparoscopy in AID failures is discussed in the light of the findings presented and the relatively low rate of post-treatment pregnancy.

Maternal serum progesterone, 17β-Estradiol and estriol are increased in pregnancies which follow treatment with human menopausal gonadotropins: Effects of multiple gestation and maternal endocrine status

A high incidence of premature labor, incompetent cervix and fetal wastage occurs in multiple gestations which follow treatment with human menopausal gonadotropins (HMG). In order to determine the effect of treatment with HMG on hormone secretion in human pregnancy, progesterone (PROG), 17 beta-estradiol (E2), estriol (E3) and human chorionic gonadotropin (hCG) were determined by radioimmunoassay in 341 serum specimens from 229 normal singleton pregnancies and in 79 serum specimens from 20 pregnancies following induction of ovulation with HMG in women with either hypothalamic amenorrhea (HA) or the polycystic ovary syndrome (PCO). Fitting equations were found for the log transformed normal values and the residuals were obtained by subtraction of the predicted normal values from the log transformed values observed in the HMG pregnancies. In pregnancies which followed treatment with HMG, PROG and E2 were initially elevated above normal. As pregnancy progressed, the deviation from normal became proportionately less. PROG (P less than 0.025) was lower and E2 (P less than 0.025) and E3 (P less than 0.05) were higher in PCO pregnancies than in HA pregnancies. Multiple gestation produced increases in PROG (P less than 0.005), E2 (P less than 0.005) and E3 (P less than 0.001) in comparison to singleton pregnancies.

The Value of Hysterosalpingography Prior to Donor Artificial Insemination

The value of hysterosalpingography as a tool in the pretreatment evaluation of candidates for donor artificial insemination has been retrospectively evaluated. In 89 consecutive artificial inseminations by donor candidates, hysterosalpingograms were evaluated for genital tract abnormalities. In only four of these studies was there a failure of dye to spill into the peritoneal cavity. The low incidence of significantly abnormal hysterosalpingographic studies, and the failure of these studies to correlate with pregnancy outcome, strongly argues against the use of hysterosalpingography in the preliminary evaluation of the patient considered for donor artificial insemination.

Evaluation of intra-amniotic administration of 120 gm of urea with 5 mg of prostaglandin F2α for midtrimester termination of pregnancy between 20 and 24 weeks' gestation

The occasional finding of signs of life in fetuses delivered following intra-amniotic administration of 80 gm of urea and 5 mg of prostaglandin F2 alpha suggested that the dose of 80 gm of urea was inadequate beyond the nineteenth week. Protocol modifications were made, and the metabolic effects of intra-amniotic administration of 120 gm of urea used beyond the nineteenth week were compared to those of the 80 gm dose of urea used in patients prior to the twentieth week. The 120 gm urea dose was well tolerated. The peak blood urea nitrogen (at 4 hours after instillation) was higher with 120 gm of urea (36.4 mg/dl) than with 80 gm of urea (24.6 mg/dl) (p less than 0.05). Small decreases in the platelet count (14% of control) and serum fibrinogen (11%), sodium (2%), potassium (7%), and carbon dioxide (11%) levels and a 5% increase in peak serum osmolality were found. Following the change in protocol, fetal heart activity has been absent at 3 hours after instillation in all cases less than 24 weeks from the last menstrual period.