William G. Dodds

Follicular stimulation for in vitro fertilization using pituitary suppression and human menopausal gonadotropins

Multiple follicular stimulation is a prerequisite to the efficient use of in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). For some individuals, however, this stimulation may be difficult using standard superovulation protocols because of dominant follicle formation, suboptimal estradiol response, or premature luteinizing hormone surge. A group of such individuals with several previous failed attempts at superovulation were studied. Follicular stimulation was accomplished using a long-acting agonist of gonadotropin-releasing hormone (GnRH) for pituitary suppression followed by human menopausal gonadotropin (hMG) for follicular stimulation. Fourteen cycles (12 IVF, 2 GIFT) were completed in 12 individuals. There were no cycle cancellations. Mean number of prior cycle cancellations per patient was 3.1 +/- 0.4. Mean number of mature oocytes recovered was 3.9 +/- 0.5. Two pregnancies resulted. Pituitary suppression with a long-acting agonist of GnRH followed by hMG appears to be an effective adjunct to current superovulation regimens.

The effect of preovulatory peritoneal fluid from cases of endometriosis on murine in vitro fertilization, embryo development, oviduct transport, and implantation*

OBJECTIVE The null hypothesis of our study is that the success of in vitro and in vivo murine fertilization and embryo development is not decreased by gamete exposure to peritoneal fluid from superovulated patients with endometriosis. STUDY DESIGN A murine in vitro fertilization model was used to test the effects of endometriosis versus nonendometriosis peritoneal fluid at concentrations of 1%, 5%, and 10% versus an unsupplemented control. Fertilization and blastocyst formation were compared by analysis of variance. In a second experiment superovulated mice were given intraperitoneal injections of endometriosis or nonendometriosis fluid or saline solution 8 hours after human chorionic gonadotropin and then mated. Some mice were killed 3 days after coitus to assess embryo number, cleavage stage, and uterine versus tubal position by means of analysis of variance and covariance with repeated measures. Others were killed 12 days after coitus with the mean number of implantations per animal between groups compared by Students t test. RESULTS In vitro fertilization rates decreased as peritoneal fluid concentration increased in both the endometriosis (65%, 43%, 33%) and nonendometriosis (65%, 52%, 35%) groups at 1%, 5%, and 10% peritoneal fluid concentration, respectively. Mice receiving intraperitoneal endometriosis or nonendometriosis fluid or saline solution injections showed no differences in embryo number, cleavage, uterine versus tubal position, or mean implantation number. CONCLUSION Peritoneal fluid from superovulated patients had no differentially negative effect when compared with the effect of nonendometriosis peritoneal fluid on murine in vitro or in vivo fertilization and embryo development, tubal embryo transport, or implantation.

Recurrent maternal virilization during pregnancy caused by benign androgen-producing ovarian lesions

Benign causes of maternal virilization in pregnancy, such as luteoma of pregnancy and hyperreactio luteinalis, are generally believed to resolve completely post partum and not to recur. We present the fifth case in the literature of recurrent maternal virilization in pregnancy. These lesions should be viewed as potentially recurrent and cases should be managed accordingly.

In vitro fertilization and embryo transfer: treatment-dependent versus -independent pregnancies.

In order to determine the true incidence of treatment-dependent versus -independent pregnancy in an in vitro fertilization (IVF) program, 274 women who underwent 492 cycles of superovulation were studied. Overall, the treatment-dependent pregnancy rate was 15%. The treatment-independent pregnancy rate was 6.6%. When a subgroup of individuals with at least one patent fallopian tube was selected for analysis, the treatment-dependent and -independent pregnancy rates were 13.9% and 11.9%, respectively. While the mean observation interval following an attempt at IVF was 2 years, 83.3% of all treatment-independent pregnancies occurred within 6 months after a trial of IVF-ET (embryo transfer). Patient characteristics that predispose to treatment-independent pregnancy are discussed.

In vitro fertilization and embryo transfer in patients with one ovary

The purpose of this investigation was to compare follicular response and pregnancy rates in patients with one and two ovaries who have undergone in vitro fertilization (IVF). No statistically significant difference was found in serum estradiol levels on the day of human chorionic gonadotropin administration, mean number of follicles (greater than 15 mm), mean total number of oocytes recovered, mean number of mature oocytes recovered, or number of pregnancies per transfer. The total number of oocytes recovered in the one- and two-ovary groups was 47 and 123, respectively. There was a significantly greater mean number of immature oocytes recovered (1.5 +/- .03 versus 0.5 +/- 0.2, P less than 0.01) and embryos transferred (2.7 +/- 0.3 versus 1.7 +/- 0.3, P less than .04) in patients with two ovaries. Though not statistically significant, a trend was noted in the two-ovary group for a greater number of pregnancies per transfer (9:25 versus 2:14). The authors conclude that single-ovary patients may have a reduced outcome with IVF compared with patients with two ovaries.

Effect of baseline ovarian cysts on in vitro fertilization and gamete intrafallopian transfer cycles

The presence of ovarian cysts may compromise the success of in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). We prospectively studied 212 consecutive ovulation induction cycles in 120 patients for IVF and/or GIFT. A baseline cyst was defined as any intraovarian cystic structure greater than or equal to 12 mm noted on ultrasonography before superovulation. Cycle outcomes were compared between patients with cysts (n = 62) versus those with no cysts (n = 150). There were no differences in follicular or luteal phase lengths or amount of human menopausal gonadotropins used. Peak estradiol (E2) levels were significantly lower and cancellation rates significantly higher in the cyst group. For noncanceled cycles, there were no significant differences in peak E2 levels, the mean number of follicles greater than or equal to 12 mm, mature oocytes retrieved, or ova transferred for GIFT or embryos for IVF. The pregnancy rates overall and for noncanceled cycles were not significantly different.

Acute effects of exercise on plasma catecholamines in sedentary and athletic women with normal and abnormal menses

Norepinephrine plays a role in the regulation of luteinizing hormone secretion and may therefore be involved in the etiology of exercise-induced menstrual dysfunction. This study evaluated both intraexercise and postexercise responses of epinephrine, norepinephrine, and dopamine in sedentary women and women runners with normal and abnormal menstruation. Five eumenorrheic nonrunners and five eumenorrheic, four oligomenorrheic, and five amenorrheic runners were evaluated on 2 consecutive days. On day 1, the women cycled on a bicycle ergometer against an increasing work load until exhaustion, and on day 2, the women underwent a submaximal exercise regimen. Serial blood draws were taken at specified time intervals during intraexercise and postexercise periods on both days. The data collected during exercise for all groups showed that epinephrine and norepinephrine had a sixfold to sevenfold rise on day 1 and had a threefold rise on day 2. Dopamine increased twofold during both exercise protocols. On day 1 norepinephrine displayed a significantly higher percentage change from baseline to peak levels for oligomenorrheic and amenorrheic runners than for eumenorrheic runners and sedentary women. This latter finding is consistent with the hypothesis that periodic marked elevations in norepinephrine levels during maximal exercise may interfere with pulsatile luteinizing hormone release and hence may play a role in the occurrence of menstrual dysfunction in women runners.

Antisperm antibodies in women undergoing intrauterine insemination

Intrauterine insemination is widely used for the treatment of infertility as a result of cervical or male factors or empirically before in vitro fertilization or gamete intrafallopian transfer. This study was designed to confirm or refute the theoretical concern that intrauterine insemination may induce antisperm antibodies in such women. Serum and cervical mucus were obtained at the first, fourth, and sixth intrauterine inseminations. The serum was screened by the Immunobead test for IgG and IgA. If screening results were positive (greater than 10% binding), antisperm antibodies were titered by the microimmobilization and microagglutination tests. The Immunobead test was performed on the cervical mucus after liquefication with bromelin. Ninety-three patients were followed up prospectively. Of these, 40 completed six intrauterine insemination cycles and the remaining 53 completed four cycles. Low transient antisperm antibody levels were detected in 10.8% of the patients and would not be expected to affect the prognosis for fertility. It is concluded that intrauterine insemination does not induce significant antisperm antibody production in women.

The effect of prolactin on murine in vitro fertilization and embryo development

Elevated levels of serum and follicular fluid prolactin occur in women undergoing ovulation induction with both clomiphene citrate and gonadotropin therapy. Prolactins effect on oocyte fertilization and embryo cleavage has not been fully characterized. Using a murine model, we investigated the effect of prolactin on in vitro fertilization and subsequent embryo cleavage in media containing 150, 400, and 600 ng/ml purified mouse prolactin. No difference was found in fertilization rates when compared with control rates. Culture of both in vivo and in vitro fertilized two-cell embryos in murine prolactin at 150, 400, and 600 ng/ml showed no significant difference in blastocyst, morula, or embryo degeneration rates when compared with control rates. An assay for binding of murine prolactin to spermatozoa, oocytes, and the embryo at various cleavage stages revealed no specific murine prolactin binding. These in vitro experimental results fail to show a role for murine prolactin in effecting mature oocyte fertilization or subsequent embryo cleavage. The lack of binding of murine prolactin to the gametes and early developing embryo supports the in vitro findings.

In vitro fertilization with concurrent pelvic reconstructive surgery.

The recent advent of ultrasound-guided follicular aspiration by various approaches now allows access to ovaries previously deemed inaccessible by laparoscopy; however, a small group of candidates for in vitro fertilization and embryo transfer (IVF-ET) require laparotomy for associated gynecologic disorders. Twenty-five IVF-ET cycles at the time of laparotomy were compared with 309 IVF-ET cycles in which oocytes were retrieved laparoscopically. Five pregnancies occurred in the IVF-ET cycle with laparotomy and one pregnancy occurred spontaneously following microsurgical tubal reconstruction. The pregnancy rate per embryo transfer was 25% in the laparotomy IVF-ET patients compared with 15.4% for the laparoscopy IVF-ET group. Obvious advantages of combining IVF-ET and pelvic reconstructive surgery include a single anesthesia exposure and economic benefits. Patients with a long history of infertility undergoing tubal reconstructive surgery may be offered combined IVF-ET. Extended anesthesia exposure with pelvic surgery demonstrated no adverse effects on the pregnancy rate.