Optimal pregnancy outcome in a minimal-stimulation in vitro fertilization program.

OBJECTIVE: We sought to provide a cost-beneficial approach to in vitro fertilization for infertile patients who could not afford the standard treatment with in vitro fertilization and to determine the optimal level of minimal ovarian stimulation to achieve acceptable pregnancy rates. STUDY DESIGN: We performed a retrospective cohort study of 216 patients who underwent "minimal stimulation" in vitro fertilization between January 1994 and December 1998. During the first half of this study, various minimal ovarian stimulation protocols were performed in our private, free-standing center for in vitro fertilization. More recently, more ovarian stimulation, including a 4-day protocol featuring gonadotropin-releasing hormone agonist flare (ultrashort flare), was used. Clinical pregnancy outcome, multiple gestation, complications, and maternal age were compared between the first and second halves of this study. RESULTS: The average ages of patients in the first half (phase 1) and the second half (phase 2) were similar, 32.4 +/- 0.3 versus 32.6 +/- 0.3 years, respectively. An average of 3.5 oocytes per retrieval was obtained in phase 1 versus 5.9 oocytes in phase 2. Failure to retrieve oocytes occurred in 3% of all cases. The mean number of embryos transferred per patient was 2.0 in phase 1 versus 2.4 in phase 2. In phase 1, 16.1% of patients failed to have viable embryos for transfer, in comparison with 9.7% in phase 2. The overall clinical pregnancy rate per retrieval was 16.9% in phase 1 versus 36. 6% in phase 2. Multiple gestation occurred in 5.0% of clinical pregnancies in phase 1 but increased to 33% in phase 2, with 9 sets of twins and 6 sets of triplets. The implantation rate was 9.3% for phase 1 versus 23.3% for phase 2. The clinical pregnancy rates per retrieval for phase 2 patients were 41.6% in women < or =34 years old and 25.6% for those > or =35 years old. No case of ovarian hyperstimulation syndrome was noted. CONCLUSIONS: Minimal ovarian stimulation in the setting of in vitro fertilization offers a cost-beneficial alternative to standard treatment with in vitro fertilization in infertile patients who are <35 years old and in women <40 years old who have adequate oocyte reserve. More stimulation improves outcome. Minimalstimulation in vitro fertilization provides an alternative for those patients who cannot afford standard in vitro fertilization or who are concerned with exposure to high dosages of fertility medications.

The pharmacology and the potential applications of GnRH antagonists.

Gonadotropin-releasing hormone (GnRH) antagonists are potent analogs of native GnRH. As biochemical probes, these recently developed compounds have allowed for profound insights into the physiology of the pituitary-ovarian and pituitary-testicular axes; as therapeutic alternatives, the GnRH antagonists hold great promise for various clinical applications, including contraception, ovulation induction, precocious puberty, and gonadal steroid-dependent neoplasia. Indeed, because of intrinsic mechanistic differences, the antagonists hold certain practical advantages over the GnRH agonists.

Reproductive performance following a second ectopic gestation.

OBJECTIVES: Our purpose was to determine the obstetric outcome following a second ectopic gestation in women actively trying to conceive, with a review of the literature. METHODS: Charts of 37 patients coded for having at least two ectopic pregnancies between 1986 and 1989 were reviewed. Duration of follow-up ranged from 7 months to 7 years with a mean follow-up time of 25 months. RESULTS: We report a 45.4% intrauterine pregnancy rate, 27.3% live birth rate, and 36.4% recurrent ectopic pregnancy rate. Review of the literature shows an intrauterine pregnancy rate of 26-50%, live birth rate of 25-31.2%, and recurrent ectopic pregnancy rate of 7.7-40%. CONCLUSIONS: Four of five studies report the risk of a third ectopic gestation is less than an intrauterine gestation. This may prove helpful in counseling patients with a history of recurrent ectopic gestation in choosing IVF or attempting conception naturally.

Ventilatory work and oxygen consumption during exercise and hyperventilation.

The work of breathing (WB), and thus the energy requirement of the respiratory muscles, is increased any time minute ventilation (VE) is elevated, by either exercise or voluntary hyperventilation. Respiratory muscle O2 consumption (VRMO2) in humans has generally been estimated by having subjects breathe at a level comparable to that during exercise while the change in O2 consumption (VO2) is measured. The difference between VO2 at rest and during hyperventilation is attributed to the respiratory muscles and is assumed to be similar to VRMO2 during exercise at the same VE. However, it has been suggested that WB differs between exercise and hyperventilation and that WB during exercise is lower than during hyperventilation at the same VE. In this study we measured WB during exercise and hyperventilation and from these measurements estimated VRMO2. WB, VE, and VO2 were measured in five male subjects during rest and during exercise or hyperventilation at levels of VE ranging from 30 to 130 l/min. VE/WB relationship was determined for both hyperventilation and exercise. Multiple regression analysis showed that the shape of the two curves was different (P < 0.0001), with WB at high levels of VE being < or = 25% higher in hyperventilation than in exercise. In a second study in which frequency, tidal volume, and duty cycle were controlled as well as VE, there was no difference in WB between exercise and hyperventilation. VO2 was significantly correlated with WB, and the estimated VRMO2 did not increase as a fraction of total VO2 as exercise intensity rose.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary function changes following exercise.

Many studies have documented differing changes in forced vital capacity (FVC) following various intensities and durations of exercise. This investigation used three different intensities and durations of treadmill running, with subjects who were active runners, with the intent of finding an intensity or duration that might elicit changes in FVC and if these changes are related to respiratory muscle fatigue. Intensities and durations included a graded maximal test to exhaustion (7-14 min); a 7-min test at 90% of maximal VO2, and a 30-min test at 60% of maximal VO2 (intensity). Maximal inspiratory pressures (MIP), maximal expiratory pressures (MEP), forced expiratory volume in 1 s (FEV1.0) and FVC were measured pretest, and 5, 10, and 30 min post-test (time). MIP was not different across time or intensities. The decrease in MEP approached significance at 10-min post-exercise compared to pretest values (P = 0.0569), with no differences found between intensities. FVC was different between times (P = 0.0117) but not between intensities. FVC was decreased at 5 and 10 min post-test compared with pre and 30 min. FEV1.0 was significantly reduced at 5 and 10 min post-test compared with pretest. These data suggest that a combination of duration and intensity may be necessary to elicit pulmonary function changes after exercise and that expiratory muscle fatigue may be a factor that results in a reduced FVC.

Ovarian steroids modulate human monocyte tumor necrosis factor alpha messenger ribonucleic acid levels in cultured human peripheral monocytes.

OBJECTIVE: To determine whether tumor necrosis factor alpha (TNF-alpha) messenger ribonucleic acid (mRNA) levels in human peripheral monocytes are regulated by ovarian steroids. DESIGN: Human granulosa-luteal cells and cultured, activated human peripheral monocytes were subjected to Northern blot analysis for TNF-alpha mRNA. SETTING: Academic research laboratory. PATIENTS: Two human female volunteers of reproductive age and in the luteal phase of the menstrual cycle. RESULTS: Human granulosa-luteal cells produce TNF-alpha mRNA. Physiological levels of progesterone (P) and estradiol (E2) modulate TNF-alpha mRNA from peripheral blood monocytes with an apparent inverse relationship between steroid concentration and TNF-alpha message. CONCLUSIONS: Progesterone and E2 at physiological concentrations regulate TNF-alpha mRNA production. The P antagonist mifepristone (RU486) and the E2 agonist/antagonist tamoxifen modulate total TNF-alpha mRNA levels, suggesting involvement of specific receptors.

Selection bias in in vitro fertilization programs.

Pregnancy rates per cycle reported from different in vitro fertilization-embryo transfer programs vary widely. While several programs have reported constant pregnancy rates per cycle, others report declining pregnancy rates. Selection biases at the point of entry and between cycles are discussed as possible explanations of these discrepancies.

Heterogeneity in patient populations explains differences in in vitro fertilization programs.

OBJECTIVE: To evaluate the efficacy of in vitro fertilization and embryo transfer (IVF-ET). DESIGN: Two different models for pregnancy rates in IVF-ET have been developed: a beta-geometric model and a split population model. SETTINGS: All IVF cycles were performed at the Yale University School of Medicine in New Haven, Connecticut. PATIENTS, PARTICIPANTS: All patients undergoing 1,257 IVF-ET cycles performed between the years 1983 through 1987. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The probability of achieving a viable pregnancy per cycle. RESULTS: Because both models provide excellent explanations for our data distribution, the decline in the conditional probability of achieving pregnancy after a given number of unsuccessful cycles may be inferred. CONCLUSIONS: These findings question the justification of continuing IVF-ET treatment beyond some threshold number of cycles.

Human follicular fluids contain tissue macrophages.

Tissue cells obtained from the follicular fluids of women undergoing in vitro fertilization and embryo transfer were found to contain interleukin-1 beta mRNA by Northern analysis. Since macrophages are known to produce interleukin-1 beta, we examined the follicular fluids of 20 women undergoing in vitro fertilization as well as tissue sections of normal human ovary for the presence of macrophages and monocytes. Although granulosa-luteal cells predominate in follicular fluid, we found that resident macrophages and monocytes comprise 5-15% of human follicular tissue cells. In addition, we observed that macrophages are present in the human ovarian follicle as well as in the corpus luteum.

Femoral neuropathy after laparoscopy. A case report.

Femoral neuropathy has been reported to occur after abdominal hysterectomies and has been related to nerve compression by abdominal wound retractors. We report a case of a 35-year-old woman with infertility who developed unilateral femoral nerve palsy after laparoscopy and hysteroscopy. This rare complication, secondary to extreme flexion, abduction and lateral rotation of the hip joint, can be prevented by careful preoperative patient positioning.

The effect of endometriomas on in vitro fertilization outcome.

To determine the effect of ovarian endometriomas on in vitro fertilization (IVF) outcome, two groups of patients were studied. Group I consisted of seven patients with ovarian endometriomas and severe pelvic adhesions treated for a total of 12 cycles. Group II patients consisted of eight patients with hydrosalpinges and comparable pelvic adhesions treated for a total of 27 cycles. There were no differences in the number of days required for stimulation or in the serum estradiol levels attained between the two groups. Group I patients were noted to have significantly fewer preovulatory follicles (1.42 vs 3.33, P less than 0.005), cycles with fertilization (28 vs 84%, P less than 0.005), and embryos transferred (0.78 vs 2.56, P = 0.01) than Group II patients. Three pregnancies occurred in Group II, while there were no conceptions among Group I patients. This study suggests that the presence of an ovarian endometrioma(s) has an adverse effect on IVF outcome and suggests that patients with ovarian endometriomas should have them removed prior to undergoing IVF.

Pelvic abscess: examination and transvaginal drainage guided by real-time ultrasonography.

We have reported a case involving a multiloculated pelvic abscess that was examined, incised, and drained under the guidance of real-time ultrasonography. This method is safe and has certain distinct advantages over more traditional surgical techniques.

Hysterosalpingography in perspective: the predictive value of oil-soluble versus water-soluble contrast media.

This study of HSG in infertile patients compares the predictive values of OSCM with WSCM, relative to the laparoscopic diagnosis. The OSCM was found to have better sensitivity and higher predictive value for pelvic disease than the WSCM. HSG and laparoscopy are adjunctive procedures, which are not mutually exclusive.

Outcome of fetal meningomyelocele after vaginal delivery.

Eight neonates with meningomyelocele were delivered vaginally. Diagnosis of meningomyelocele was made by ultrasonography during the latter half of pregnancy in three patients. The remaining five did not have ultrasound examination during the antenatal period. None of the meningomyelocele sacs (less than or equal to 4 cm in diameter) was ruptured at the time of delivery. Cesarean section may not be necessary for all fetuses with meningomyelocele.

Cytosol estrogen receptor content of female parietal peritoneum.

The ovarian and peritoneal mesothelium are believed to derive from the same embryonal coelomic epithelium. Neoplastic proliferation of these epithelia is sometimes grossly and histologically similar. Recently estrogen receptors have been identified in gynecologic neoplasms. With the use of standard techniques, the parietal peritoneum was assessed for estrogen receptor content in 17 women undergoing celiotomy for various reasons. All peritoneal specimens were negative for estrogen receptor content. This suggests a heterogeneous origin of the peritoneal surface epithelium and that peritoneum may not be müllerian in origin.