Hormonal strategies of the menopause.

A woman at the age of 50 in the United States has a life expectancy of approximately 30 years. The menopausal years, the symptoms associated with menopause, and concurrent conditions associated with these age groups are of major importance, since women may live up to one third of their lives in menopause. In this discussion, the physiologic conditions associated with menopause, including osteoporosis, cardiovascular disease, and breast cancer, are considered, with specific assessment of risks and benefits of hormone replacement therapy. Specific hormone replacement regimens are reviewed, along with non-estrogenic approaches to osteoporosis therapy. The long-term benefits of estrogen on female life expectancy are reviewed, balancing cardiovascular and osteoporosis benefits within the context of long-term effects on breast cancer risk.

Effect of incremental time experience on the results of in vitro fertilization with intracytoplasmic sperm injection (ICSI).

PURPOSE: Our objective was to determine the effect of experience on the results with intracytoplasmic sperm injection. METHODS: The quarterly outcome with both ICSI and traditional in vitro fertilization (IVF) in 1994 was analyzed in 475 patients under age 40 undergoing 595 oocyte retrievals. The data represent 307 patients undergoing 379 retrievals for IVF and 165 patients undergoing 216 retrievals for ICSI. RESULTS: Fertilization rates with ICSI improved significantly each quarter (52.96, 62.17, 70.17, and 74.87% in Q-I, Q-II, Q-III, and Q-IV, respectively), while the rate with IVF improved significantly between Q-I (69.9%) and Q-II (80.10%) and slightly but significantly between Q-II and Q-IV (82.88%). The implantation rate per embryo after ICSI improved significantly after Q-I (6.17%) compared to Q-II (10.70%) and Q-IV (12.14%). The pregnancy rate per transfer with ICSI increased steadily after Q-I (13.79, 21.88, 23.53, and 25.00% in Q-I through Q-IV), reaching statistical significance between Q-I and Q-III and between Q-I and Q-IV. CONCLUSIONS: Although acceptable results can be obtained with ICSI after a relatively short period of time, optimum results require substantial experience.

Deleterious effect of the presence of hydrosalpinx on implantation and pregnancy rates with in vitro fertilization.

OBJECTIVE: To determine the effect of the presence of a unilateral or bilateral hydrosalpinx on the outcome with IVF-ET. DESIGN: Retrospective analysis of clinical and laboratory data. SETTING: Hospital-based private IVF center. PATIENTS: Eight hundred forty-six patients with tubal disease younger than age 40 years undergoing 1,766 stimulation cycles. In 118 cycles, a hydrosalpinx was noted sonographically (group I) whereas, in 1,648 cycles, no such image was documented. MAIN OUTCOME MEASURES: Pregnancy and implantation rates. RESULTS: Group I displayed a significantly lower pregnancy rate per transfer than group II (16.84% versus 36.83%) and a lower implantation rate (3.92% versus 11.53%). CONCLUSION: The presence of hydrosalpinx adversely affects the outcome of IVF.

Hydrosalpinx affects the implantation of previously cryopreserved embryos.

The presence of hydrosalpinx has been reported to negatively affect the pregnancy and implantation rate after in-vitro fertilization (IVF) with embryo transfer. Hydrosalpinges are able to enlarge during ovarian stimulation with a possible increased passage of tubal fluid into the endometrial cavity. We report the effect of hydrosalpinges during the transfer of previously cryopreserved/thawed embryos during a natural cycle. In all, 14 transfers in 0 patients with a sonographically-documented hydrosalpinx during the studied cycle (group I) were compared to 98 cycles in 74 patients with tubal disease but no such sonographic finding (group II). Both pregnancy and implantation rates were significantly lower in group I (7.14 versus 24.49% and 5.0 versus 10. 8% respectively). The presence of hydrosalpinx negatively affects pregnancy and implantation rates during natural cycles.

Perforated appendicitis and ectopic pregnancy following in-vitro fertilization.

This report describes a case of perforated appendicitis and ectopic pregnancy following in-vitro fertilization (IVF) and embryo transfer. Perforated appendicitis was a coincidental event following IVF and embryo transfer. Immediate diagnosis and treatment of the perforated appendicitis saved the life of the patient. The ectopic pregnancy was completely resolved with two doses of methotrexate administration.

Pathophysiology and management of endometriosis.

Endometriosis is a common disease that affects up to 5 million women in the United States. Specifically the prevalence of endometriosis is 1 in 15 (7%) women of reproductive age, and there is an associated incidence of infertility in as many as 30% to 40% of cases. The precise physiologic mechanism for the development of endometriosis lesions in the pelvis and abdominal cavity has not been elucidated. Substantial evidence exists, however, that endometriosis is dependent on estrogen for continued growth and proliferation. Therefore, suppression of the hypothalamic-pituitary-ovarian axis with analogues of a gonadotropin-releasing hormone is being increasingly undertaken. Since the most effective resolution of endometriosis occurs after oophorectomy or onset of menopause, the hypoestrogenic state induced by GnRH analogues is of major significance for patients with active disease. Medical therapy for endometriosis is often used as primary therapy for symptomatic disease or as an adjunct to surgical management of pelvic pain or infertility.

The effect of epidermal growth factor in human granulosa cells varies with follicle size.

EGF decreases aromatase activity and stimulates the proliferation of granulosa cells. To determine if EGF affects follicles of different maturity differently, human granulosa cells obtained from 6 patients at the time of IVF were pooled according to size and cultured in serum free medium with or without EGF. Estrogen production at 72 h was determined by measuring tritiated water formed in a 1-h culture with 1 beta [3H] androstenedione. The change in estrogen production with EGF was compared for cells from the smallest and largest follicles for each patient. Estrogen production in response to EGF decreased with increasing follicular size in all six observations. EGF may mediate luteinized granulosa cell aromatase activity in vivo, and may be a factor responsible for the relative decline in estrogen production in the preovulatory follicle.

Maternal characteristics of women delivered of twins: natural vs. induced.

This study retrospectively compared sociodemographic and anthropometric data, as well as selected obstetric outcomes, of 13 mothers of twins who conceived after ovulation induction with clomiphene citrate or Pergonal with similar data from 255 mothers who conceived naturally. Infertile women were significantly (P < .011) older and likely to be married, of the white race, and more educated than women who conceived naturally. Treated women were also taller and heavier prior to conception (NS). Treated women gained significantly more weight (45.9 lb vs. 30.1 lb). They also had a higher proportion of gestations > 32 weeks (91.7% vs. 74.1%) and longer mean gestations (36.5 weeks vs. 35.4 weeks) compared to naturally conceiving mothers of twins, but neither of these differences was significant. The infants of treated mothers had birthweights 9.5% heavier than the infants of mothers who conceived naturally. These retrospective findings suggest that previously infertile women who conceive twins do not suffer worse reproductive outcome than women who conceive naturally.

A comparison of the reproductive outcome between women with a unicornuate uterus and women with a didelphic uterus.

OBJECTIVE: To compare the reproductive performance of women with a unicornuate uterus with the reproductive performance of women with a didelphic uterus. DESIGN: Retrospective. SETTING: Reproductive endocrinology service of a tertiary referral hospital. MAIN OUTCOME MEASURES: The proportion of pregnancies resulting in spontaneous abortion, preterm delivery, term delivery, and living children was determined for each group. RESULTS: Twenty-nine women with a unicornuate uterus and 25 women with a didelphic uterus were identified. Twenty women with a unicornuate uterus produced a total of 40 pregnancies, whereas 13 women with a didelphic uterus produced a total of 28 pregnancies. The 33% spontaneous abortion rate in the unicornuate group was not significantly different from the 23% rate in the didelphic group. The proportion of pregnancies resulting in preterm delivery, term delivery, and living children was similar in both groups. CONCLUSIONS: The reproductive performance of women with a unicornuate uterus is similar to the performance of women with a didelphic uterus.

Superovulation with or without intrauterine insemination for the treatment of infertility.

Patients undergoing human menopausal gonadotropin (hMG) superovulation were reviewed retrospectively to determine whether fecundity was greater for intrauterine insemination (IUI) than timed intercourse. Forty patients with unexplained infertility, American Fertility Society I or II endometriosis, luteal phase defect and/or cervical factor were treated with hMG alone or hMG plus IUI. Twenty-eight underwent 52 cycles of hMG/IUI, and 19 underwent 31 cycles of hMG. The probability of pregnancy after four cycles was significantly better in the hMG/IUI group (.90) than the hMG group (.37, P = .049). There was a 54.5% multiple pregnancy rate, and one patient was admitted to the hospital for hyperstimulation. When traditional therapy fails, hMG/IUI significantly increases the pregnancy rates as compared to hMG with timed intercourse in a "good prognosis" group of patients.

Time-related effects of gonadotropin-releasing hormone analog treatment in experimentally induced endometriosis in the rat.

The purpose of our study was to characterize the time-dependent effect of gonadotropin-releasing hormone analog (GnRH-a) therapy on endometriosis explant using the rat model. Endometriosis was induced in 60 mature female rats. One group of treated animals as well as controls were killed at 2, 4, 6 and 8 weeks of treatment at which time the explant was evaluated. Explant volume was significantly reduced in all treatment groups, an effect that was more significant in animals treated for greater than or equal to 4 weeks compared with those treated for only 2 weeks. We conclude that GnRH-a treatment caused gradual regression of endometrial explant that was effectively complete by 4 weeks of treatment. We further conclude that this experimental model may be useful in the evaluation of other modes of endometriosis therapy.

Laparoscopic cautery in the treatment of endometriosis-related infertility.

Life table analysis and the two-parameter exponential method have been applied to pregnancy rates in 72 patients undergoing laparoscopic cautery exclusively. Patients with male factor infertility were excluded. Estimated cure rates for patients with stage I and II disease were 98.2% and 76.6%, respectively (not significantly different). No significant difference was seen when anovulation complicated the endometriosis (68.6%). When greater than one infertility factor was present, a significant difference was observed (50.6%). Patients with stage I disease had an average fecundity of 10.30% with decreasing values observed in stage II (7.59%), anovulation (6.67%), and more than one infertility factor (3.33%). We conclude that laparoscopic cauterization is an effective mode of therapy for the treatment of stage I and II endometriosis associated with infertility.

The incidence of human immunodeficiency virus (HIV) in fetal cord samples utilized as serum supplements for in vitro fertilization.

Prior to initiating routine fetal cord serum (FCS) supplementation in our in vitro laboratory, the incidence of HIV in 306 random fetal cord samples obtained at the Labor and Delivery Unit of the Johns Hopkins Hospital from July 1985 to January 1988 was determined from a cross-sectional patient sample. Of 306 samples, 3 (0.98%) were positive for HIV, and confirmed by Western blot analysis, enzyme immunoassay (ELISA), a prevalence significantly higher than a national sample (0.012%). The use of FCS in this setting was determined to be an unacceptable risk to patients undergoing in vitro fertilization. The 90-day quarantine period for verification of HIV seronegativity applied to semen donors may not be applicable to FCS sampling. Patient risk may also increase with pooling of FCS samples prior to HIV testing.

Induction of ovulation and pregnancy following lateral oophoropexy for Hodgkin's disease.

Present therapy for Hodgkin's disease which primarily affects young patients may produce long term remissions in more than 50% of cases. Potential injuries to the reproductive system from radiation or chemotherapy are significant considerations in therapeutic planning. Assessment of the effects of infradiaphragmatic radiation on germ cells may avoid ovarian ablation in women of reproductive age. This report addresses ovarian function and fertility following lateral oophoropexy and repositioning for Hodgkin's disease.

Neosalpingostomy for distal tubal obstruction: prognostic factors and impact of surgical technique.

We reviewed the clinical records of all women who underwent microsurgical terminal neosalpingostomy for distal tubal obstruction between January 1983 and June 1988. We identified 95 women whose preoperative evaluation revealed no other contributory factors for infertility and analyzed their pregnancy outcome after this procedure. Pregnancy success was inversely related to the extent of tubal distortion (dilation, rugal integrity, and status of the fimbria) and degree of adnexal adhesions. Using our classification system for distal tubal obstruction, patients with mild disease had an 80% pregnancy rate, whereas patients with moderate and severe disease had a 31% and 16% success rate, respectively. We found no statistically significant difference in pregnancy outcome when we compared this series with our previous group, reported in 1978, where contemporary microsurgical technique was not used. Although we feel that optimal surgical technique is important to maximize success, we conclude that the most important prognostic factor in pregnancy outcome after neosalpingostomy for distal tubal disease is the anatomical and functional integrity of the tube.

Effect of serum from patients with minimal to mild endometriosis on mouse embryo development in vitro.

Two-cell mouse embryos were cultured at 37 degrees C in 5% CO2, 95% air with a 7.5% serum supplement from patients with minimal to mild endometriosis, (group I, n = 31), tubal factor (group II, n = 33), male factor (group III, n = 17), fetal cord samples (group IV, n = 37), and Ham's F-10 medium (Gibco, Grand Island, NY) without a serum supplement (group V, n = 30). The progression to blastocyst stage (mean percent +/- SE) at 96 hours in groups I, II, III, IV, and V was 29.9% +/- 3.7%, 60.6% +/- 4.9%, 56.2% +/- 5.2%, 61.7% +/- 5.8%, and 63.2% +/- 6.9%, respectively. Serum factors appear to be associated with an inhibition of early embryogenesis, which may explain the decreased fertility rates observed in patients with minimal to mild endometriosis.

Time trends in risk factors and clinical outcome of ectopic pregnancy.

Ectopic pregnancy (EP) admissions at The Johns Hopkins Hospital were reviewed for 160 patients admitted from 1970 to 1974 and 253 patients from 1980 to 1984. Over the decade, average annual admissions for EP increased by 64%, and a higher proportion of cases in 1980 to 1984 were unmarried women with no insurance coverage. There were significant increases in cases with a history of sexually transmitted diseases (from 19.1% to 31.6%) and in recurrent EPs (7.6% to 19.0%) but declines in EP associated with contraceptive failures. Newer diagnostic techniques such as quantitative serum human chorionic gonadotropin assays, pelvic ultrasound, and laparoscopy were more frequently used in the 1980 to 1984 period, resulting in less severe morbidity on admission, more conservative surgical management, and reduced length of hospitalization. Thus, although admissions for EP have increased, the severity of illness has been reduced by earlier diagnosis and more conservative management.

Current technology of in vitro fertilization and embryo transfer.

Since the initial human in vitro fertilization (IVF-ET) procedure in 1978, the laparoscope was the primary method for oocyte collection. Although laparoscopic retrieval instrumentation has been refined, ultrasound-guided follicular puncture has become the major retrieval technique in IVF-ET repertoire. The Johns Hopkins In Vitro Fertilization Program was initiated in 1984, recording the first in vitro pregnancy in Maryland.

Megestrol acetate for treatment of endometriosis.

Between 1977-1989, 29 women with symptomatic endometriosis were treated with megestrol acetate by the Johns Hopkins Division of Reproductive Endocrinology. All had previously received one or more alternative medical treatments for endometriosis, in each case discontinued because of poor response or development of unacceptable side effects. Treatment consisted of a daily dose of 40 mg megestrol acetate orally for up to 24 months. Disease-related symptoms (dysmenorrhea, noncyclic pelvic pain, and dyspareunia) were relieved in 86% of the subjects treated with an adequate course of therapy. Side effects were fairly well tolerated, although eight women discontinued treatment within 2 months and two others stopped the drug by 4 months. These preliminary findings suggest that megestrol acetate may be an effective treatment for patients with endometriosis, even those who have been unresponsive to other modes of therapy.