Merle J. Berger

Tubal Infertility and the Intrauterine Device

To study the association between intrauterine devices (IUDs) and pelvic inflammatory disease, we compared contraceptive histories in 4185 while women--283 nulliparous women with primary tubal infertility, 69 women with secondary tubal infertility, and 3833 women admitted for delivery at seven collaborating hospitals from 1981 to 1983. The relative risk of tubal infertility associated with IUD use was calculated by means of multivariate logistic regression to control for confounding factors, including region, year of menarche, religion, education, smoking, and reported number of sexual partners. The adjusted risk of primary tubal infertility associated with any IUD use before a first live birth was 2.0 (95 per cent confidence limits, 1.5 to 2.6) relative to nonuse. Users of the Dalkon Shield had an adjusted risk of 3.3 (1.7 to 6.1), users of the Lippes Loop or Saf-T-Coil had a risk of 2.9 (1.7 to 5.2), and users of copper IUDs had a risk of 1.6 (1.1 to 2.4). Women who reported having only one sexual partner had no increased risk of primary tubal infertility associated with IUD use. The adjusted risk of secondary tubal infertility associated with use of a copper IUD after a first live birth was not statistically significant (1.5; 95 per cent confidence limits, 0.8 to 3.0), whereas the risk from similar use of noncopper devices was significant (2.8; 1.3 to 5.9). We conclude that tubal infertility is associated with IUD use, but less so with copper IUDs.

The effectiveness of danazol on subsequent fertility in minimal endometriosis

Sixty-five patients with minimal endometriosis were studied for the purpose of prospectively comparing conservative medical management in the form of danazol with no therapy in the treatment of this disease. After completion of the basic infertility evaluation and correction of additional factors affecting fertility, a diagnostic laparoscopy, dilatation and curettage (D and C), and tubal lavage were performed. A randomly selected cord determined whether the patient received no treatment for 6 months or danazol for 6 months followed by no treatment for 6 months. The dosage of danazol was 800 mg daily for the first 2 months, 600 mg daily for the next 2 months, and 400 mg daily for the final 2 months. The mean age of both the danazol-treated group and the group that received no danazol was 31 years. Conception occurred in 30% of the danazol-treated patients and 50% of the untreated patients. These results suggest that infertile patients with minimal endometriosis should be given an opportunity to conceive after laparoscopy, D and C, and tubal lavage. This would seem particularly true in older patients where a 6-month delay in permitting attempts at conception represents a significant interval of time.

The association between smoking and female infertility as influenced by cause of the infertility

Smoking histories were compared in 901 women with infertility of different types and 1264 women admitted for delivery at seven collaborating hospitals. The relative risk for infertility associated with cigarette smoking prior to the infertility diagnosis for nulliparous cases or first live birth for controls was calculated using a multivariate logistic-regression model to control for potential confounding factors, including center, age, religion, education, number of sexual partners, and contraceptive use. The adjusted risk for infertility attributed primarily to cervical factor (n = 96) was 1.7 (P = 0.04), to tubal disease unrelated to endometriosis (n = 225) was 1.6 (P = 0.009), to ovulatory factor (n = 389) was 1.0 (not significant [NS]), and to endometriosis (n = 191) was 0.9 (NS). The authors conclude that cigarette smoking is significantly associated only with certain types of primary female infertility.

Simultaneous intrauterine and tubal pregnancies following ovulation induction

Abstract Two cases of simultaneous intrauterine and tubal pregnancies resulting from the administration of human menopausal gonadotropin (HMG) in one instance and clomiphene citrate in the other are described. No vaginal bleeding or spotting was observed, and dilatation and curettage were not performed around the time the tubal pregnancies were excised; consequently, the intrauterine pregnancy was salvaged in each instance.

Reversal of persistent anovulation in polycystic ovarian disease by administration of chronic low-dose follicle-stimulating hormone

Low doses of follicle-stimulating hormone (FSH) were administered once daily to two consecutive patients with polycystic ovarian disease (PCOD) for therapy of infertility. Serial blood samples were obtained for gonadotropins and ovarian steroid determinations during the period of FSH administration. Exogenous FSH resulted in an initial and concomitant decrease in serum androstenedione (A), estrone (E1), and luteinizing hormone (LH), with an increase in estradiol (E2) and FSH. Subsequent changes in the above-mentioned hormonal levels were typical of a normal ovulatory cycle, with the exception of FSH, which continued to rise in the second half of the follicular phase. This was attributed to the exogenous administration of FSH. Both patients became pregnant in their first induced ovulatory cycle by administration of chronic low-dose FSH. These preliminary data demonstrate (1) a correction of the biochemical imbalance characteristic of PCOD, (2) successful ovulation induction, and (3) restoration of fertility in PCOD treated with chronic low-dose FSH.

The role of ultrasound in ovulation induction: a critical appraisal *

Twenty-five cycles induced by human menopausal gonadotropin (hMG) were serially studied by ultrasound. The developing follicles were observed up to and beyond human chorionic gonadotropin (hCG) administration. Ovulation as determined by subsequent pregnancy or a sustained elevation of basal temperature was seen in 18 of these cycles. Among these patients the follicular size ranged between 24 and 13 millimeters. No pregnancies occurred where the follicular size was below 15 mm. A shortened luteal phase was noted in three cycles where the follicular size was either 13 or 14 mm. Multiple follicles greater than 10 mm were observed in 14 of the ovulating cycles, but in no case did a multiple pregnancy occur. Fifteen millimeters is therefore suggested as a minimum size for satisfactory ovulation, but it does not appear that an optimum size exists. We conclude that ultrasound can play an important role in the monitoring of ovulation induction but does not replace the present methods.

Multivariate Analysis of Factors Predictive of Successful Live Births in In Vitro Fertilization (IVF) Suggests Strategies to Improve IVF Outcome

Purpose:Our purpose was (1) to identify characteristics correlated with pregnancy outcome, (2) to use these characteristics to predict in vitro fertilization (IVF) outcome, and (3) to develop strategies that might improve IVF success.Methods:Maternal age, cause for IVF, donor insemination, rank of attempt, serum estradiol and luteinizing hormone levels on the day of human chorionic gonadotropin administration, flexible vs rigid catheter, number of embryos transferred of each morphologic type, and cell number were analyzed by logistic regression.Results:Variables positively correlated with success are as follows: (1) for pregnancy, endometriosis and 2-, 3-, and 4-cell good and 4-cell excellent embryos: (2) for live births, 2-, 3-, and 4-cell good and 4-cell excellent embryos and donor insemination; and (3) for multiple births, 2- and 4-cell good and 4-cell excellent embryos. Maternal age was negatively correlated with live births.Conclusions:Embryos derived from IVF have different potentials for implantation, live births, and multiple births. Transferring one additional good-quality embryo for each 5 years of incremental increase in maternal age is predicated to improve live birth rates without increasing multiple births.

The role of luteinizing hormone in human follicular maturation and function.

Abstract In an attempt to elucidate the role of luteinzing hormone (LH) in the normal menstrual cycle and in gonadotropin therapy, the effects of follicle-stimulating hormone (FSH) with and without LH on the same amenorrheic patient were compared. The first treatment cycle consisted of FSH alone and was ineffective in producing either an estrogen response or ovulation despite high peripheral levels of FSH. When FSH together with LH was administered in the second cycle, one third as much FSH and lower peripheral FSH levels were effective in producing a marked increase in urinary estrogens and apprent ovulation, indicating that LH is necessary to induce maturation of the ovarian follicle in human beings.

Estrogen monitoring and the prevention of ovarian overstimulation during gonadotropin therapy

Abstract The results of therapy with human menopausal gonadotropin (HMG) was compared in patients controlled by the development of fern formation with patients monitored by daily total estrogen excretion. The percentage of anovulatory cycles and pregnancies were high with both methods. There were less multiple pregnancies and cases of ovarian enlargement when estrogen monitoring was utilized. Of most significance was the fact that there were no cases of triplet pregnancy or cases of massive ovarian enlargement with or without ascites when estrogen monitoring was utilized.

Microscopic epididymal sperm aspiration (MESA): A new option for treatment of the obstructive azoospermia associated with cystic fibrosis

Cystic fibrosis is a life-threatening disease. Only recently has the prognosis improved. In the male patient there is an almost invariable absence or maldevelopment of the vas deferens, creating a situation of obstructive azoospermia. Consequently, their fertility potential has been considered nonexistent. Having gained experience in microscopic epididymal sperm aspiration coupled with the advanced reproductive technologies for the treatment of congenital absence of the vasa, we sought to extend this treatment option to the male cystic fibrosis population. An Indian male with clinically evident and genetically confirmed cystic fibrosis underwent microscopic retrieval of epididymal sperm. The anatomy of the epididymis and the quality of sperm obtained were similar to those patients with congenital absence of the vas deferens. After appropriate spousal genetic testing, superovulation, and transvaginal oocyte retrieval, in vitro insemination of sperm was performed. Fifty percent of the oocytes were subjected to partial zona dissection and a single embryo resulted. Subsequent to transfer, no conception was realized but the effort expanded the clinical usefulness of microscopic epididymal sperm aspiration. This should open up an avenue of treatment for couples in whom only the most dire predictions for fertility have been made to date.