Maria F. Hayes

Comparison of different treatment modalities of endometriosis in infertile women

This study was designed to evaluate the effectiveness of three therapeutic modalities in the management of stage I and II endometriosis. Management modalities consisted of (1) no treatment (controls, n=56); (2) oral medroxyprogesterone acetate (MPA), 30mg orally per day for 90days (n =36); and (3) danazol, 600 to 800mg daily for 6months (n =52). All patients were followed for at least 18months of exposure to pregnancy. Cumulative pregnancy rates were determined by life-table analysis. At 30months, pregnancies resulted in 55% of group I (controls), 71% of group II (MPA), and 46% of group III (danazol). There were no significant differences among these rates. Similarly, there was no significant difference between the cumulative pregnancy rates for stage I (59%) and for stage II (57%). Abortion rates for the various treatment modalities were the following: MPA 6.3%, danazol 11%, and no treatment, 14.3%. The spontaneous abortion rate in stage I and stage II disease was not significantly different. The results of this study suggest that a period of expectant management with correction of other infertility factors may be warranted in patients with mild to moderate endometriosis before medical therapy is contemplated.

Follicular fluid concentrations of thiopental and thiamylal during laparoscopy for oocyte retrieval

Because access into ovarian tissue of drugs used during anesthesia may be potentially harmful to the oocyte and/or follicular structure, we measured concentrations of thiopental (n = 15) and thiamylal (n = 9) in follicular fluid (FF) aspirates of 24 patients who underwent laparoscopic oocyte retrieval. In both groups, measurable amounts of the respective drug were found in all FF aspirates. Within individual patients, plasma concentrations of both drugs declined during the period of sampling between initial and final follicular aspiration. The mean plasma drug concentration was 7.99 +/- 3.97 micrograms/ml in the thiamylal group and 4.13 +/- 0.90 micrograms/ml in the thiopental group. Mean drug concentrations in FF were similar in both groups (thiopental 1.62 +/- 0.61 micrograms/ml; thiamylal 1.67 +/- 0.83 micrograms/ml). The mean FF/plasma concentration ratio during the sampling period was greater in the thiopental group (0.41 +/- 0.19) as compared with the thiamylal group (0.22 +/- 0.14). Several steps in the clinical management of these patients can be taken to reduce exposure of oocytes to drugs used during anesthesia.

Experience with intrauterine insemination for cervical factor and oligospermia

: In the past 100 years, interest in intrauterine insemination for cervical factor has waxed and waned. Recently the advent of in vitro fertilization, with improved methods of sperm washing and preparation, has revived interest in intrauterine insemination as a modality for the treatment of infertility. Twenty-seven couples with infertility resulting from cervical factor and/or oligospermia were entered into our intrauterine insemination protocol. A total of 107 intrauterine inseminations were performed in 85 menstrual cycles. Nineteen couples with a cervical factor as the major factor in their infertility experienced three pregnancies (16%). The remaining eight couples who had oligospermia with or without cervical factor produced no pregnancies. No major complications occurred from this procedure. In view of the low pregnancy rate experienced in this study, we must seriously question the value of intrauterine insemination in the treatment of cervical factors and/or oligospermia.

Is intraperitoneal dextran 70 safe for routine gynecologic use

The routine use of intraperitoneal 32% dextran 70 has been suggested as an adjuvant to prevent postsurgical pelvic adhesions. Two hundred thirty-four women received an antiadhesion regimen consisting of intraperitoneal 32% dextran 70, dexamethasone, and promethazine. Ten women (4%) experienced spontaneous leakage of the dextran-peritoneal fluid mixture through their abdominal incisions. Painless bilateral swelling of the labia was noted in 18 women (8%). Mild abdominal bloating and weight gain of from 2.5 to 11 pounds were common. No anaphylactic reactions, peritonitis, or wound infections were experienced by any woman. Intraperitoneal dextran 70 appears to be a safe, well-tolerated antiadhesion adjuvant for routine use in gynecologic operations.

Use of spinal anesthesia in laparoscopy for in vitro fertilization

Regional anesthesia, in selected cases, is a useful alternative method of providing anesthesia for the retrieval of oocytes when general anesthesia is not indicated. We report our experience in managing anesthesia in four patients in whom we used a subarachnoid block. Ova were obtained in three patients, and two became pregnant and delivered healthy full-term infants. Although the high pregnancy rate was noted with delight, it is clearly a statistical happenstance. It would be interesting, however, to carry out prospective studies to determine whether a relationship between the incidence of pregnancy and anesthetic method might exist.

Correlation of serum estradiol levels and ultrasound monitoring to assess follicular maturation

Thirty-eight patients underwent 38 cycles of induction of ovulation using stepwise human menopausal gonadotropin and human chorionic gonadotropin (hCG) administration. Ultrasonography was performed on the day of hCG injection. The mean age +/- standard error of the mean (SEM) of the patients was 32.9 +/- 0.8 years, and the duration of infertility ranged from 1 to 14 years (median, 2.8). Ultrasonographic measurements were obtained of the largest diameter and the volume of the dominant follicles as well as all other follicles in both ovaries. Data were analyzed by Students t-test, regression analysis, and analysis of variance. The mean +/- SEM diameter of dominant follicles was 1.8 +/- 0.1 cm, and the volume of dominant follicles was 3.5 +/- 0.8 cm. The mean +/- SEM serum estradiol (E2) level before hCG administration was 659 +/- 62 pg/ml. Significant correlations were found between preovulatory serum E2 levels and the total follicular volume of both ovaries (r = 0.41, P less than 0.05) and follicular volume of the ovary containing the dominant follicle (r = 0.42, P less than 0.01). No significant correlation was observed between the diameter of the dominant follicle and serum E2 levels. These results suggest that ultrasound findings reflect growth, whereas serum E2 levels primarily detect functional activity of follicles.

Human follicular fluid: prolactin is biologically active and ovum fertilization correlates with estradiol concentration

The bioactivity of prolactin (PRL) in follicular fluid (FF) obtained from mature preovulatory follicles was measured by the Nb2 lymphoma-cell bioassay and compared with the immunoreactivity as measured by radioimmunoassay (RIA-PRL). There was a good correlation between the two assay systems (P<0.01), and when RIA-PRL was more than 25 ng/ml, both assay systems yielded comparable values, with a mean bioassay/RIA ratio of 1.06±0.03; however, when RIA-PRL was 25 ng/ml or less, a discrepancy between the two assay systems was evident, with a bioassay/RIA ratio of 1.55±0.15. The estradiol (E2) concentration of FF obtained from follicles that contained oocytes which were subsequently fertilized was greater than that in follicles containing oocytes which were not fertilized: 588±62 vs 376±37 ng/ml (P<0.01), respectively. No differences were found in bioassay-PRL, RIA-PRL, progesterone (P), and FF volumes between fertilized and unfertilized groups of follicles. FF from mature preovulatory follicles contained greater concentrations of RIA-PRL compared to immature follicles (34.6±3.1 vs 8.5±1.6 ng/ml; P<0.001).

Clinical value of prolactin bioassay in euprolactinemic reproductive disorders

To examine the disparity between clinical presentation and prolactin (PRL) measured by radioimmunoassay (RIA), serum samples from 128 patients with galactorrhea and/or reproductive disorders were evaluated by RIA for immunoassayable PRL (RIA-PRL) and by Nb2 lymphoma cell proliferation assay for bioassayable PRL (bioassay-PRL). One hundred fifteen patients had normal RIA-PRL and 13 patients had high RIA-PRL (greater than 25 ng/ml). Twenty patients had galactorrhea, two of whom had hyperprolactinemia. The reproductive disorders in female patients included infertility, amenorrhea, oligomenorrhea, irregular menstrual cycles, and luteal phase defects. Six oligospermic males also were studied. Twenty-three male and female volunteers with no evidence of reproductive disorders served as controls. Appropriate comparisons showed that PRL bioassay/RIA ratio, an index of agreement between the two assay systems, did not differ for the various patient groups compared with controls. It is concluded that Nb2 lymphoma bioassay does not provide additional diagnostic value to RIA in defining the cause of euprolactinemic galactorrhea and/or reproductive disorders.

Comparison of Different Treatment Modalities of Endometriosis in Infertile Women

This study was designed to evaluate the effectiveness of three therapeutic modalities in the management of stage I and II endometriosis. Management modalities consisted of no treatment (controls, n = 56); oral medroxyprogesterone acetate (MPA), 30 mg orally per day for 90 days (n = 36); and danazol, 600 to 800 mg daily for 6 months (n = 52). All patients were followed for at least 18 months of exposure to pregnancy. Cumulative pregnancy rates were determined by life-table analysis. At 30 months, pregnancies resulted in 55% of group I (controls), 71% of group II (MPA), and 46% of group III (danazol). There were no significant differences among these rates. Similarly, there was no significant difference between the cumulative pregnancy rates for stage I (59%) and for stage II (57%). Abortion rates for the various treatment modalities were the following: MPA 6.3%, danazol 11%, and no treatment, 14.3%. The spontaneous abortion rate in stage I and stage II disease was not significantly different. The results of this study suggest that a period of expectant management with correction of other infertility factors may be warranted in patients with mild to moderate endometriosis before medical therapy is contemplated.

Correlation and comparison of Nb2 lymphoma cell bioassay with radioimmunoassay for human prolactin**Supported in part by NIH grant HD-14571 (to R. R. G.).

Serum samples from groups of men and women with normal and elevated prolactin (PRL) levels were assayed by radioimmunoassay (RIA) and by Nb2 lymphoma cell bioassay (BA) for the presence of PRL. Because the Nb2 lymphoma cells respond to both PRL and growth hormone, BA for PRL activity was carried out before and after neutralization of growth hormone in the serum samples. There were excellent correlations between RIA and BA both in euprolactinemic (r = 0.7587; P less than 0.002) and hyperprolactinemic (r = 0.9558; P less than 0.001) subjects. On an absolute basis, RIA and BA values were similar in the euprolactinemic group (6.6 +/- 0.8 versus 6.2 +/- 1.0), whereas in the hyperprolactinemic group, RIA values were significantly higher than the BA results (89.41 +/- 22.4 versus 62.1 +/- 21.2). The two assay systems also appeared to correlate better in women who were hyperprolactinemic, with obvious menstrual cycle disturbances, than in hyperprolactinemic women without menstrual cycle disturbances.