The luteal phase after ovulation induction with human menopausal gonadotropin and one versus two doses of a gonadotropin-releasing hormone agonist.

OBJECTIVE: To use a GnRH agonist (GnRH-a) to induce ovulation after priming with exogenous hMG. DESIGN: Prospective, randomized double-blind protocol using one or two doses of intranasal nafarelin. SETTING: Office-based ovulation induction program. PATIENTS, INTERVENTIONS: Infertile women not conceiving after use of clomiphene citrate for at least 6 months who were given hMG and nafarelin. No luteal support was given. MAIN OUTCOME MEASURES: Serum concentrations of FSH, LH, E2, and P acutely and at 6 days after GnRH-a administration. Duration of the luteal phase was assessed. RESULTS: Ovulation with elevation of both FSH and LH was achieved. The two-dose regimen was more effective than one dose for sustained LH release. Luteal phase P values and luteal phase duration were both less than usually seen with gonadotropin hCG therapy in the absence of luteal phase support. CONCLUSIONS: Ovulation induction with GnRH-a after hMG priming produces unacceptable luteal phase cycles in the absence of hormonal support.

Serial beta-subunit human chorionic gonadotropin doubling time as a prognosticator of pregnancy outcome in an infertile population.

Prospective evaluation through the use of radioimmunoassay of the beta-subunit of human chorionic gonadotropin (beta-hCG) in blood samples obtained during the first 30 days of gestation was performed on an infertile population at high risk for pregnancy loss. Four hundred and fourteen samples in 281 pregnancies were analyzed. On the basis of single, random beta-hCG samples in asymptomatic patients, 77% of successful pregnancies and 59% of abortions were correctly identified. On the basis of beta-hCG doubling time (mean 2.2 days +/- 1.0 [2 SD]) computed from serial sampling, again in asymptomatic patients, 88% of successful pregnancies and 76% of abortions were correctly identified. beta-hCG doubling time appears to provide a reliable method of evaluating early pregnancy prognosis with significantly greater ability to identify problem pregnancies within the first 30 days of gestation than does single random hCG values.

The human sperm-hamster egg penetration assay: prognostic value.

Males from 227 infertile couples were evaluated using the human sperm-hamster egg penetration assay (SPA). Indications for the SPA were abnormal semen analyses, poor postcoital tests, documented autologous sperm antibodies, and long-term unexplained infertility. Normal results defined as greater than or equal to 11% penetration were seen in 58.6% of couples. Penetration rates of 1% to 10% were observed in 25.6%, and 15.9% failed to penetrate any of the oocytes. During the follow-up period, with a mean of 17.9 months, 26.9% conceived at least once with or without treatment. Monthly fecundity was 0.014 for normal SPA patients and 0.007 for the abnormal SPA group when calculated by the Kaplan-Meier survival curve with Cox correction for unequal follow-up. The monthly fecundity rate at any time during the 30-month interval of follow-up was twice as great for men with normal SPA values as for those with abnormal values, regardless of male or female diagnosis or therapy indicating the prognostic value of the SPA in an infertile population.

Insemination data on men with varicoceles.

OBJECTIVE: To determine possible benefits of sperm processing and intrauterine insemination (IUI) for a group of men with a varicocele history who had not achieved a pregnancy by natural coitus (mean duration of infertility 42.2 months). DESIGN: A retrospective study including infertile men with varicoceles who were classified by their semen analyses and sperm penetration assays (SPAs). SETTING: Private practice of infertility. PATIENTS: Seventy-one infertile couples. The husbands had a varicocele history and were grouped into four clinical categories (14 untreated, 5 medical treatment, 34 varicocelectomies, and 18 varicocelectomies plus medical treatment). The wives were studied or treated before IUI. INTERVENTIONS: Varicocelectomies were performed on the males when indicated. Female studies included laparoscopies as indicated intrauterine insemination with Tomcat catheter (Sherwood Medical, St. Louis, MO) was performed in all cases. MAIN OUTCOME MEASURES: Overall pregnancy rates (PRs) and fecundity rates with sperm processing and IUI. RESULTS: Six pregnancies occurred with 66 cycles of sperm processing and IUI among 28 men with normal SPAs (PR 21%, fecundity rate = 0.09). In contrast, there were no pregnancies with 121 cycles among 43 varicocele patients with abnormal SPA results or with low values for all three semen parameters. CONCLUSIONS: Sperm processing and IUI may be beneficial for selected patients with varicoceles who had not achieved a pregnancy by coitus.

Leuprolide acetate-prepared in vitro fertilization-gamete intrafallopian transfer cycles: efficacy versus controls and cost analysis.

OBJECTIVE: To evaluate the effect of gonadotropin-releasing hormone agonist (GnRH-a) when given through stimulation with gonadotropins versus stopping it as stimulation was initiated versus a control group unprepared in this manner. Also, to construct a cost analysis for this type of therapy in an in vitro fertilization-gamete intrafallopian transfer program (IVF-GIFT). DESIGN: Prospective, consecutive, randomized, with a control group. SETTING: An out-patient IVF-GIFT program. PATIENTS: One hundred new patients entering an IVF-GIFT program. INTERVENTIONS: In vitro fertilization or GIFT cycles with or without preparation (pituitary suppression) by GnRH-a administration in which suppression was continued or halted as gonadotropins were begun. MAIN OUTCOME MEASURES: Cancellation rates, ampules, and days of gonadotropin use, costs, estradiol (E2) level, egg numbers and quality, and pregnancy rates. RESULTS: Stopping GnRH-a (leuprolide acetate) therapy as stimulation was begun did not lessen the suppressive effect in reduction of spontaneous luteinizing hormone surge as seen with continued use of agonist. In contrast, the control group had a 30.3% cancellation rate before ovum retrieval. The E2 and egg data among the groups were similar, but as expected, agonist use led to the need for more and longer duration of gonadotropin stimulation. Pregnancy rates were not different by group. Costs were approximately even by the third initiated cycle.

Sex selection by sperm separation and insemination.

The Ericsson albumin filtration technique was used to collect a fraction rich in Y sperm for selective insemination in couples desiring a male infant. Of 35 conceptions in which sex was known at delivery or spontaneous abortion, there were 28 males (80%). Twelve pregnancies were achieved after separation of sperm in a Sephadex gel filtration system designed to allow for collection of a fraction enriched in X sperm. Seven pregnancies have resulted in females, two in males, and one in twins of each sex. One patient aborted, and one is still pregnant. While selection for either sex can be done electively, on the basis of sociologic preference, female selection has, as an additional indication, avoidance of male offspring to carriers of sex-linked diseases.

Is paracervical block anesthesia for oocyte retrieval effective?

OBJECTIVE: To quantitate pain relief associated with paracervical local anesthesia during transvaginal ultrasound-guided collection. DESIGN: The study was a prospective, randomized, double-blinded, placebo-controlled, and no treatment-controlled investigation. Pain scores for vaginal pain associated with entry into the cul-de-sac and global assessment for the entire procedure were generated separately by patient and physician. Variables evaluated include duration of procedure, patient weight and age, total number of vaginal and ovarian "follicular" punctures, number of oocytes retrieved, and amount of IV medication. SETTING: A private IVF-ET program. PATIENTS: Women in an IVF-ET program who volunteered to join the study (n = 101). INTERVENTIONS: Local anesthesia as a paracervical block compared with placebo or no injection during transvaginal oocyte retrieval, with all patients receiving IV sedation. RESULTS: Both vaginal and global pain scores, whether patient or physician assessed were lower for paracervical block than placebo. Agreements between physician and patient assessments of pain scores were close. Duration of the procedure was correlated with pain score. In general, a placebo effect on pain perception compared with no injection was not seen. CONCLUSION: Paracervical local anesthesia compared with placebo injection was associated with lower pain scores for both vaginal puncture and global assessment of the oocyte retrieval process but was not significantly better than no injection for global evaluation.

Predicting success of gamete intrafallopian transfer.

OBJECTIVES: To examine seminal parameters predictive for success in a cycle of GIFT and to construct an algorithm using pertinent seminal data as well as easily obtained historical data to predict pregnancy and viable pregnancy rates. DESIGN: A retrospective study of 544 cycles in 376 couples. SETTING: A private IVF-ET and GIFT center. PATIENTS: Couples in a GIFT program with a mean of 53.6 months of infertility who had failed to conceive with other therapies. INTERVENTIONS: Gamete intrafallopian transfer. MAIN OUTCOME MEASURES: Pregnancy as a function of laboratory historical data with emphasis on seminal parameters. RESULTS: Motility was the only seminal parameter that was predictive. Success was correlated with the number of oocytes returned and inversely related to female age. An algorithm to predict pregnancy in a GIFT cycle as well as viable pregnancy was constructed. CONCLUSIONS: Motility is the only seminal parameter predictive for success in a GIFT cycle. An easily programmable algorithm can be constructed to help patient and physician decide on the appropriateness of GIFT for each couple.

Outcome in 242 in vitro fertilization-embryo replacement or gamete intrafallopian transfer-induced pregnancies.

Two centers combined data on 152 in vitro fertilization embryo replacement and 90 gamete intrafallopian transfer generated pregnancies. The outcomes of the pregnancies with respect to abortion, ectopic gestation, and multiple gestation were evaluated independently by method and by center. Only with multiple gestation by center was a difference seen. Variables examined included estradiol levels, luteal phase support, maternal age, and prior reproductive history, and the number of eggs or embryos replaced.

Correlations between results of the immunobead test and the sperm penetration assay.

Immunobead testing (IBT) and human sperm-hamster egg penetration assay (SPA) were performed in 233 infertile men. Positive immunologic results were recorded in 31 (13.3%). Significant reduction in SPA scores was found in patients with IgG antisperm antibodies alone but not in patients with IgA alone or in combination with IgG. Normal SPA scores were seen in 56% of immunonegative patients (n = 113) vs. 32% of immunopositive patients (n = 10). Therefore, a normal SPA does not rule out the presence of significant levels of antisperm antibodies.

Pregnancy despite continued elevation of prolactin levels while on bromergocryptine.

A case of long standing secondary amenorrhea with hyperprolactinemia and pregnancy success despite inability to normalize prolactin levels with high doses of bromergocryptine is presented.

Measurements of androgenicity. The spectrum of progestogen activity.

The problem with applying information on progestogen potency obtained from biologic testing to clinical prescribing practices is that the changes in potency relate to more than progestogen dosage. The spectrum of progestogen activity is discussed, with an emphasis on the effects of the progestogens used in oral contraceptive therapy.

Ultrasonic indices of ovulation.

Ultrasound affords direct observation of anatomic changes leading to ovulation. It is useful in many clinical applications, such as monitoring ovulation induction regimens, determining the time of oocyte harvest in in vitro fertilization programs and assisting with timing artificial insemination. The specific time of ovulation cannot be predicted accurately enough using ultrasound to make it optimal for routine monthly cycle use.

Formulation and noncontraceptive uses of the new, low-dose oral contraceptive.

Although contraceptive efficacy is the major reason for using oral contraceptives (OCs), other physiologic changes occur with them that can be beneficial to patients. The new, low-dose OCs are of particular interest in this regard.

PIP: Whether the differences in progestin-estrogen formulations of oral contraceptives (OCs) lead to any clinically significant differences is an important question, even though the concept of "tailoring the pill to the patient" has assumed less importance as the hormonal dosages have decreased. Each component can be evaluated individually, but it is often difficult to predict the result of their combined action. All of the new low-dose formulations contain the same estrogen, ethinyl estradiol (EE). Although the type of progestin in low-dose OCs is probably of little significance for efficacy and cycle control, it may be more important in regard to lipid and carbohydrate metabolism. Combined OC therapy acts simultaneously at various levels of the reproductive system, and contraceptive efficacy of pills with less than 50 mcg of estrogen probably results from these combined actions. The action of estrogen and progesterone is synergistic: the sustained estrogen component exerts negative feedback on gonadotropin secretion, provides stability to the endometrium, and increases the potency of the progestational agent, while progestin can influence only estrogen-primed tissue. The progestin suppresses luteinizing hormone secretion; in addition, progestational influence dominates estrogenic influence in affecting the remainder of the reproductive system. Previous OC usage may delay pregnancy by several months but does not impair longterm fertility potential or increase congenital anomalies or abortions if conception occurs subsequent to the 1st post-pill cycle. Breakthrough bleeding, which occurs in 15% of users, is the single most frequent cause of pill discontinuation but appears to be of no medical consequence. Breakthrough bleeding and amenorrhea may be controlled by changing the pill formulation. Depression has been reported in 5% of OC users, but pill use appears to alleviate premenstrual tension. The individual patient's risk-benefit ratio must be considered when noncontraceptive uses of the pill are contemplated. OC use has been cited as a cure for dysmenorrhea, although the mechanism is uncertain. The possible preservation of fertility or prevention of progression of endometriosis with cyclic pill use should be investigated. The controlled sloughing of a uniformily thinning endometrium prevents and controls dysfunctional uterine bleeding, endometrial hyperplasia, and the anemia that results. Use of OCs has been recommended in treatment of hirsutism to suppress ovarian function when the hypersecretion of androgens is documented. Since both adrenal and ovarian androgens are often involved in hirsutism, the combined suppressive actions of OCs frequently are beneficial. Estrogens also decrease sebum production and often result in indirect acne improvement. Cyclic estrogen-progesterone therapy is recommended for inducing sexual maturation in primary amenorrhea secondary to gonadal failure.

Ectopic pregnancy. A review of the etiologic factors.

Ectopic pregnancy was experienced by 103 women in our practice, for a total of 123 such pregnancies. These patients' histories were reviewed in an attempt to identify certain risk factors. The ectopic pregnancies were diagnosed prior to rupture in 73% of cases. Patients were followed for subsequent reproductive function. Among the 96 who were not sterilized during or after surgery for ectopic pregnancy, intrauterine pregnancy was achieved by 34, while 15 had at least one additional ectopic gestation. Risk factors were identified. Different surgical approaches to the affected tube influence future reproductive function and repeat ectopic gestation.

Diagnostic techniques used for ectopic pregnancy.

Though all diagnostic techniques used for ectopic pregnancy yield false-negative and false-positive results, prospective serial studies using hormonal and sonographic testing are quite accurate when appropriately applied.

Early urinary pregnancy testing. Correlation with serum beta-HCG radioimmunoassay.

Urinary pregnancy testing with Sensitex, a tube macroflocculation system, produced a positive test by 17 days after basal-body-temperature-timed ovulation in 59% of determinations. Data from days 18 to 21 showed that a negative test was associated with a statistically significantly increased propensity for first-trimester abortion. Freezing of the urinary specimens, but not refrigerated sm, produced a positive test by 17 days after basal-body-temperature-timed ovulation in 59% of determinations. Data from days 18 to 21 showed that a negative test was associated with a statistically significantly increased propensity for first-trimester abortion. Freezing of the urinary specimens, but not refrigerated storage for five days, adversely affected the accuracy of the test.

A comparison of serial quantitative serum and urine tests in early pregnancy.

Serial urinary beta human chorionic gonadotropin (beta-hCG) immunoassay was performed on 60 patients during early pregnancy. Results were expressed as tube dilutions positive and were compared with quantitative serum beta human chorionic gonadotropin radioimmunoassay (beta-hCG-RIA) values. The parallel rise of human chorionic gonadotropin (hCG) measured by serum beta-hCG-RIA and a macroflocculation beta-specific urinary immunoassay in early pregnancy was confirmed. The ability of each to predict abortion prior to the onset of patient symptoms or clinical signs of disturbed gestation was quantitated. Results were expressed for each method according to standard regression lines or doubling time for individuals. Utilizing either statistical method, urinary testing was as accurate as serum testing for the prediction of normal pregnancy (about 90% for each). Serum testing was 78% correct in predicting abortion; urinary testing was 63% accurate.

Laparoscopic approach to definitive treatment of androgen insensitivity syndrome. A case report.

Androgen insensitivity syndrome is the most common form of male pseudohermaphroditism. This report describes a laparoscopic approach to diagnosis and gonadectomy in a patient with androgen insensitivity syndrome in whom the intraabdominal gonadal location was uncertain.

Obesity and GnRH action. Report of a case with contribution by peripherally derived estrogens.

BACKGROUND: Gonadotropin-releasing hormone agonists (GnRH-a) are effective in reducing the pituitary release of gonadotropins, which, in turn, decrease ovarian steroidogenesis. The resulting menopausal state decreases the volume and vascular supply to uterine leiomyomas. Peripheral adipose tissue also contributes significantly to the circulatory estrogen pool, which is formed independent of pituitary function. As such, obesity may interfere with depot leuprolide acetate effects, allowing normal estrogen levels despite gonadotropin suppression. CASE: A premenopausal, morbidly obese woman was referred for treatment of menorrhagia and uterine leiomyomas. Despite administration of depot leuprolide, a GnRH-a, she continued to bleed heavily. Serum estradiol levels remained in the normal range, with suppression of follicle-stimulating hormone (FSH) levels. The desired hypoestrogenic effect from GnRH-a administration was thought to be negated by estradiol levels arising from peripherally derived conversion of adrenal androgens in adipose tissue. A GnRH stimulation test was performed to evaluate the responsiveness of the pituitary to the above therapy. While FSH was suppressed and unresponsive to stimulation, estradiol remained unchanged. CONCLUSION: Peripheral production of estrogen appears to be unaffected by leuprolide administration. Consideration should be given to the patient's body habitus when administering a GnRH suppressant. Morbidly obese patients possess an unlimited reservoir for peripheral estrogen synthesis.