Gonadotropin-releasing hormone agonist use in assisted reproduction cycles: the influence of long and short regimens on pregnancy rates.

OBJECTIVE: To compare the efficacy of GnRH agonists used in either the flare (short) or down-regulation (long) regimen as part of IVF or GIFT treatment cycles. DESIGN: Observational study. SETTING: Three IVF clinics. PATIENT(S): One thousand two hundred forty-four couples accepted for IVF or GIFT treatment at participating clinics. INTERVENTION(S): In vitro fertilization or GIFT protocols standard to each clinic were recorded. MAIN OUTCOME MEASURE(S): Treatment cycle characteristics and outcomes, including E2 level, number of oocytes retrieved, and clinical pregnancy rate. RESULT(S): At site 1, there were 146 clinical pregnancies in 980 flare cycles, for a pregnancy rate of 14.9%, compared with 148 clinical pregnancies in 650 down-regulation cycles, for a pregnancy rate of 22.8%. This difference persisted after adjustment for age, primary infertility diagnosis, GIFT or IVF therapy, and year of treatment, and appeared to be mediated largely by the number of oocytes retrieved (mean, 9.8 for downregulation and 8.7 for flare in the first cycle). Despite having fewer oocytes retrieved, women who received flare regimens had higher E2 levels before hCG administration. CONCLUSION(S): Women who received GnRH agonists in a flare regimen had 11% fewer oocytes retrieved and a 35% reduction in the clinical pregnancy rate compared with those who received them in a down-regulation regimen; this difference was not explained by patient selection factors.

Successful pregnancies with the use of laminaria tents before embryo transfer for refractory cervical stenosis.

OBJECTIVE: To determine whether laminaria tents are a safe and effective method of cervical dilatation in patients with a history of cervical stenosis and difficult ET. DESIGN: Case reports describing two patients. SETTING: Tertiary care, assisted reproduction practice. PATIENT(S): Two patients with cervical stenosis and a history of multiple failed cycles of IVF. INTERVENTION(S): Laminaria tents were placed intracervically before ET. MAIN OUTCOME MEASURE(S): Presence of a gestational sac and fetal heartbeat on ultrasound. RESULT(S): Successful clinical pregnancies occurred in both patients after laminaria placement and ET. CONCLUSION(S): Laminaria tent cervical dilatation appears to be a safe and effective option to assist ET in patients with a history of cervical stenosis.

The effects of baseline ovarian cysts on the clinical response to controlled ovarian hyperstimulation in an in vitro fertilization program.

The purpose of this study was to examine the effects of baseline ovarian cysts on the clinical response to controlled ovarian hyperstimulation (COH) in an in vitro fertilization (IVF) program. Patients were divided into two groups: group 1 (n = 21) had cysts with mean diameters between 10 and 45 mm on their baseline ultrasound before COH, and group 2 (n = 76) had no ovarian cysts on their baseline ultrasound. There was no statistically significant difference between the groups in maximum serum estradiol, the number of follicles greater than or equal to 10 mm on the day of human chorionic gonadotropin (hCG) injection, the number of follicles greater than or equal to 15 mm on the day of hCG injection, the number of oocytes retrieved, and the number of embryos transferred. There was no difference between the groups in the cycle cancellation rate, in the pregnancy rate per cycle, or in the pregnancy rate per embryo transfer. This study suggests that small baseline ovarian cysts do not negatively impact on ovulation induction parameters or pregnancy rates in an IVF program.

Effects of previous ovarian surgery on the follicular response to ovulation induction in an in vitro fertilization program.

This study examined the effects of previous ovarian surgery on the clinical response to ovulation induction with clomiphene citrate-human menopausal gonadotropin in an in vitro fertilization program. Patients were divided into five clinical groups: group A (n = 63), no previous ovarian surgery; B (n = 9), unilateral cystectomy; C (n = 6), unilateral oophorectomy with no contralateral ovarian surgery; D (n = 7), bilateral ovarian surgery with both ovaries present; and E (n = 4), unilateral oophorectomy and contralateral cystectomy. Patients in group E demonstrated significantly lower serum estradiol on cycle days 9-11 (P less than or equal to .05) and fewer follicles on cycle days 11-12 (P less than or equal to .05) than did patients in groups A-D. The percentage of cancelled cycles increased with increasing amounts of ovarian surgery (P less than or equal to .03). The study suggests that one cause of a poor response to ovulation induction for in vitro fertilization may be prior extensive ovarian surgery.

In vitro fertilization, GIFT and related technologies--hope in a test tube.

In vitro fertilization (IVF) is demanding, expensive and inefficient. Nevertheless, tens of thousands of couples have undertaken the procedure because of their intense desire to have a biological child. Modifications of the current IVF process--simplification of ovulation induction and prediction of successful cycles; use of ultrasound instead of laparoscopy for egg retrieval; freezing of excess embryos for later replacement; and the substitution of GIFT (gamete intra-fallopian transfer) for IVF when it is indicated--may increase its acceptability to couples and improve success rates. Meanwhile, IVF has had tremendous impact on our understanding of fertility and should help physicians in their approach to infertility in the future. It has also ushered in a new era of genetic engineering whose potential we have not yet begun to realize.

Constituents of cigarette smoke inhibit human granulosa cell aromatase.

Recent epidemiologic studies suggest that women smokers have lower endogenous estrogen levels than nonsmokers. The effects of aqueous extracts of cigarette smoke on aromatase were evaluated in cultures of human granulosa cells. Aqueous extracts of cigarette smoke inhibited the conversion of androstenedione (delta 4A) to estradiol in a dose-dependent manner. Dialysis experiments demonstrated that 90% of the inhibitory activity of aqueous extracts of cigarette smoke was in the less than 1000 mol wt fraction. Removal of the aqueous extract of cigarette smoke from the culture medium resulted in a complete reversal of the inhibition of delta 4A aromatization. Addition of supraphysiologic concentrations of delta 4A (73 microM) to the culture medium blocked the smoke-induced inhibition of aromatization. Two low-molecular-weight components of cigarette smoke, nicotine and anabasine, inhibited granulosa cell aromatase in a dose-dependent manner. These studies suggest that constituents of cigarette smoke inhibit a major steroidogenic pathway.

Cellular immunity to sperm in infertile women.

To investigate further whether immunity to sperm contributes to some cases of infertility in women, the production of leukocyte inhibitory factor by blood mononuclear cells challenged with human sperm in vitro was measured in women with infertility associated with poor results of postcoital tests or long-term unexplained infertility. Five (36%) of 14 infertile patients but none of nine fertile volunteers responded significantly to sperm in this assay. No study subject had serum IgG or IgM antibodies to sperm detected. These data provide additional evidence consistent with the possibility that cellular immunity to sperm-specific antigen(s) functions in the primary pathogenesis of infertility in some women.

Maternal and perinatal morbidity resulting from placenta previa.

One hundred forty-seven cases of partial or complete placenta previa from 1975 to 1982 were reviewed. A history of prior cesarean section was associated with a significant increase in maternal morbidity, including massive hemorrhage, placenta accreta, and hysterectomy. Despite tocolysis and transfusions to delay delivery, nearly two-thirds of the patients were delivered before 36 weeks' gestation. Onset of bleeding before 20 weeks' gestation was associated with a very poor fetal prognosis. The perinatal mortality rate was 81 of 1000. The overall incidence of respiratory distress syndrome was 22%; this was a major cause of neonatal mortality and morbidity. There was a statistically significant correlation between antepartum maternal hemorrhage and the need for neonatal transfusion, and between the neonatal anemia and the amount of intrapartum maternal blood loss.

Conversion of progesterone to corticosteroids by the midterm fetal adrenal and kidney.

Midterm fetal adrenal and kidney tissue homogenates were incubated with 3H-progesterone (1 microM) and its conversion to te 3H-corticosteroids metabolites studied. Cortisol (36.3%) and corticosterone (4.7%) were isolated from the adrenal, and 11-deoxycortisol (32.5%) and deoxycorticosterone (21.1%) from the kidney. The results of these incubations confirmed the presence of 17- and 21-hydroxylase activities in both fetal tissues, and that of 11 beta-hydroxylase activity only in fetal adrenal tissue. We conclude that during pregnancy when progesterone levels are high, biosynthesis by the fetal kidney of 11-deoxycortisol, the most abundant corticosteroid formed by this tissue in this investigation, might provide to the fetal adrenal an important precursor for cortisol biosynthesis within the fetal compartment.

Pregnancy outcomes following Tompkins metroplasty.

Eighteen patients with poor reproductive histories and 2 patients with primary infertility underwent Tompkins metroplasty for a septate uterus. There were 19 pregnancies within 2 years of surgery, and 11 patients had at least 1 viable pregnancy, for an overall success rate of 55%. One of the infertile patients conceived and delivered. The average fecundability rate for the first 24 months was 0.078 (normal, 0.20). The cumulative pregnancy rate at 27 months was 94% by the life-table method. The group of patients (n = 14) with two or more losses and no other major risk factors for reproductive failure had higher fecundability and a better success rate (71%). The Tompkins metroplasty is a technically simple procedure with a success rate similar to that of the Jones procedure.