The impact of hydrosalpinx on successful pregnancy in tubal factor infertility treated by in vitro fertilization.

OBJECTIVE: To determine the impact of hydrosalpinx on pregnancy rates in patients undergoing IVF for infertility caused by tubal disease. DESIGN: Review of the records of all patients who had undergone IVF for tubal factor infertility at our institution between May 1988 and October 1994. SETTING: A university-sponsored, hospital-based IVF facility. PATIENT(S): Two hundred fifty patients were identified with infertility due to tubal disease; 67 of these had at least one documented hydrosalpinx whereas the remaining 183 did not. MAIN OUTCOME MEASURE(S): Numbers of oocytes retrieved and fertilized, the number of embryos transferred and implanting, and resulting pregnancy rates. RESULT(S): The groups were similar in age and cycle cancellation rates. The patients with hydrosalpinx had greater numbers of oocytes retrieved per cycle (15.0 versus 11.6) and embryos transferred per cycle then those without hydrosalpinges (4.21 versus 3.98). The hydrosalpinx group also undertook more cycles per patient (2.31 versus 1.96). Fertilization rates between the two groups were similar, but implantation rates were decreased in those with hydrosalpinx (8.5% versus 11.2%). CONCLUSION(S): Hydrosalpinx did not result in impaired ovarian stimulation or decreased oocyte fertilization. It did, however, interfere with implantation and reduce to some degree the success of IVF in achieving an ongoing pregnancy. The validity of routine salpingectomy for hydrosalpinx is debatable, but its use in selected individuals may well be appropriate.

5alpha-reductase 1 and 2 expression and activity in human ovarian follicles, stroma and corpus luteum as compared to neonatal foreskin.

5alpha-Reductase is the steroidogenic enzyme which reduces testosterone to 5alpha-dihydrotestosterone. In the human two different enzymes have been described, 5alpha-reductase 1 and 2. The present investigations were undertaken to determine whether 5alpha-reductase 1 and 2 were expressed in the human ovary, and to determine the relative activity of the two enzymes in various ovarian tissues. The ovary apparently expressed mRNA for only 5alpha-reductase 1, whereas the foreskin expressed both 5alpha-reductase 1 and 2. We compared the 5alpha-reductase activity at both pH 5.5 (optimum for 5alpha-reductase 2 activity) and 8.0 (optimum for 5alpha-reductase 1 activity). 5alpha-reductase activity of foreskin at pH 5.5 was 3900 times higher than small follicles, 1500 times higher than ovarian stroma, and 240 times higher than corpora lutea (all P < 0.01). 5alpha-reductase activity of corpora lutea at pH 5.5 was 17-fold higher than that of follicles (P < 0.01) and 6.5-fold higher than that of ovarian stroma (P < 0.05). 5alpha-Reductase activity of foreskin at pH 8.0 was 93 times higher than small follicles, 51 times higher than corpora lutea, and 170 times higher than ovarian stroma (all P < 0.01). The ratio of 5alpha-reductase activity at pH 5.5 to that at pH 8.0 was higher in foreskin than in corpus luteum (P < 0.05), ovarian stroma (P < 0.01), or ovarian follicles (P < 0.01). The ratio was lower in ovarian follicles than in stroma or corpus luteum (both P < 0.05).

Effects of fetal number and multifetal reduction on length of in vitro fertilization pregnancies.

OBJECTIVE: To determine the effects of multifetal reduction and other variables on the duration of gestation of in vitro fertilization (IVF) pregnancies. METHODS: All 274 IVF pregnancies from the inception of the Women and Infants' Hospital IVF Program on May 26, 1988, until December 31, 1993, were evaluated. RESULTS: Spontaneous reduction occurred in ten pregnancies, and multifetal reduction was elected in 28 multiple gestations. Among 260 pregnancies that remained viable beyond 20 weeks, 162 singletons (37.9 +/- 0.29 weeks; mean +/- standard error) had a longer mean gestation than did 64 twins (34.6 +/- 0.61 weeks), 25 pregnancies reduced to twins (33.4 +/- 1.0 weeks), or nine triplets (29.7 +/- 1.9 weeks). Triplets delivered 4.9 weeks earlier than nonreduced twins (P < .05) and 3.7 weeks before twins resulting from multifetal pregnancy reduction (P < .05). Regression analysis showed that at the 8-week ultrasound, each viable fetus could be expected to reduce the duration of the gestation by about 3.6 weeks, and each fetus reduced medically or as a result of natural causes could be expected to prolong the gestation by approximately 3.0 weeks. Only 14% of triplet pregnancies underwent spontaneous multifetal reduction. CONCLUSION: Multifetal reduction of pregnancies with three or more fetuses was beneficial and increased the duration of gestation.

The effect of ovulation induction on the concentration of maternal serum relaxin in twin pregnancies.

OBJECTIVE: Our purpose was to determine the effects of fetal number, various ovulation induction treatments, and placental hormones on the concentration of maternal serum relaxin. STUDY DESIGN: The concentrations of relaxin, human chorionic gonadotropin, estriol, and alpha-fetoprotein were determined in blood samples drawn at 16 to 18 weeks for prenatal diagnosis in 72 singleton and 115 twin pregnancies and analyzed by one-way analysis of variance, correlation analysis, and stepwise multiple linear regression of the log-transformed data. RESULTS: The maternal serum concentrations of each of the four measured hormones were significantly higher in the twin pregnancies than in the singleton pregnancies: 1.4-fold for relaxin, 1.9-fold for human chorionic gonadotropin, 1.9-fold for estriol, and 2.2-fold for alpha-fetoprotein (all p < 0.01). The concentrations of each of the four hormones were significantly correlated with each of the others and with the number of fetuses (p < 0.01), except that estriol was not significantly correlated with human chorionic gonadotropin. The serum relaxin concentration in twin pregnancies after treatment with follicle-stimulating hormone and luteinizing hormone (menotropins) (n = 10) was 3.3-fold that in twins resulting from spontaneous ovulation (n = 89, p < 0.01). In twins resulting from in vitro fertilization or gamete intrafallopian transfer (n = 9) the serum relaxin concentration was 2.6-fold higher than in twins resulting from spontaneous ovulation (p < 0.01). The effect of clomiphene citrate (1.2-fold, n = 7) failed to reach statistical significance. CONCLUSIONS: The second fetus causes a 1.4-fold increase in the concentration of maternal serum relaxin in twin pregnancies. Induction of ovulation with menotropins causes an additional 3.3-fold increase, whereas in vitro fertilization or gamete intrafallopian transfer treatment causes an additional 2.6-fold increase over that seen in twin pregnancies that followed spontaneous ovulation.

Relaxin secretion in in vitro fertilization pregnancies.

OBJECTIVE: This study was designed to determine whether the late luteal functional status of the corpora lutea in in vitro fertilization cycles alters the secretion of relaxin during pregnancy. STUDY DESIGN: Analysis of serum relaxin, human chorionic gonadotropin, and steroid concentrations in sera of women with pregnancies viable beyond the twelfth week as a result of in vitro fertilization treatment was performed. RESULTS: The serum estradiol and progesterone concentrations decreased 5.5- and 4-fold from days 5 to 6 after human chorionic gonadotropin to days 11 to 13 after human chorionic gonadotropin, respectively. The serum relaxin concentration increased 8-fold between the 11- to 15-day interval and the 16- to 50-day interval after human chorionic gonadotropin and another 6-fold to the 51- to 90-day interval after human chorionic gonadotropin (all p < 0.01). Multiple linear regression analysis showed that the serum estradiol level 11 to 13 days after human chorionic gonadotropin and the serum human chorionic gonadotropin level 11 to 15 days after human chorionic gonadotropin were the most powerful paired predictors of the concentration of serum relaxin measured in the 11- to 15-day interval after human chorionic gonadotropin interval (R2 = 0.39, n = 50), the 16- to 50-day interval (R2 = 0.61, n = 51), and the 51- to 90-day interval (R2 = 0.55, n = 39). CONCLUSION: Secretion of relaxin is determined by an interaction of the late luteal functional status of the corpora lutea and the human chorionic gonadotropin secreted by the implanting pregnancy. These data allow for the hypothesis that inducing functional luteolysis by substituting one or more injections of luteinizing hormone for the human chorionic gonadotropin injection may decrease secretion of steroids, relaxin, and other factors from the corpora lutea during pregnancy, decreasing the risk of premature delivery in multiple gestations and the ovarian hyperstimulation syndrome.

Maternal and neonatal morbidity associated with in vitro fertilization.

OBJECTIVE: The purpose of this case-control study was to examine the maternal and neonatal morbidities associated with in vitro fertilization (IVF) in a single large teaching hospital. It was hypothesized that IVF mothers would have more perinatal complications and IVF infants would have higher mortality and morbidity rates than non-IVF control subjects. METHODS: One hundred forty-three gestations resulting from 101 IVF pregnancies, which included singletons (n = 62), twins (n = 72), and triplets (n = 9), were compared with equal numbers of non-IVF control subjects. Each pregnancy was matched by maternal age, race, insurance type, neonatal gender, order of gestation, order in delivery, and date of delivery (+/- 6 months). Among the 143 matched gestations, six IVF and seven control infants died, leaving 137 IVF and 136 control neonates for comparison. RESULTS: The IVF mothers had more pregnancy-induced hypertension (21% vs 4%), premature labor (44% vs 22%), labor induction (25% vs 1%), and preterm delivery (37% vs 21%). The IVF infant survivors had a lower mean (+/- SD) birth weight (2623 +/- 857 gm vs 3006 +/- 797 gm), more frequent occurrence of low birth weight (42% vs 27%), and shorter gestations (37 +/- 4 vs 38 +/- 3 weeks). The IVF infants had longer hospitalizations, more days of oxygen therapy, more days of continuous positive airway pressure, and increased prevalence of respiratory distress syndrome, patent ductus arteriosus, and sepsis. CONCLUSIONS: Couples who undergo IVF appear to be at increased risk of having low birth weight and preterm infants, and multiple gestations account for most of the neonatal morbidities. Both the mothers who conceive multiple gestations by means of IVF and their neonates are at an increased risk of having multiple morbidities.

Follicular fluid insulin-like growth factor-I and insulin-like growth factor-II concentrations vary as a function of day 3 serum follicle stimulating hormone.

We determined follicular fluid concentrations of insulin-like growth factor (IGF)-I, IGF-II and inhibin as a function of day 3 serum follicle stimulating hormone (FSH) in 16 women undergoing follicular fluid aspiration in preparation for in-vitro fertilization and embryo transfer. Follicular fluid concentrations of IGF-I and IGF-II were significantly less in the 'low' FSH group as compared to the 'high' FSH group. The mean IGF-I concentration was 67.6 ng/ml [confidence intervals (CI) 51.6-92.5] in the 'low' FSH group compared to 87.1 ng/ml (CI 72.8-104.2; P < 0.025) in the 'high' FSH group. Mean IGF-II concentrations were 354.8 ng/ml (CI 297.8-422.9) in the 'low' FSH group compared to 489.8 ng/ml (CI 384.6-624.5; P < 0.05) in the 'high' FSH group. Follicular fluid inhibin concentrations did not differ between groups. These differences in follicular fluid IGF as a function of day 3 FSH may raise questions regarding the role growth factors play in the physiological processes of the ageing follicle.

Low maternal serum unconjugated estriol during prenatal screening as an indication of placental steroid sulfatase deficiency and X-linked ichthyosis.

Placental sulfatase deficiency is an X-linked metabolic defect that occurs in about 1 in 2,000 to 5,000 males. It is associated with congenital ichthyosis. In this report, the authors document a case of placental sulfatase deficiency detected during routine prenatal screening of maternal serum by the triple test: serum alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG). At 16-weeks gestation, her AFP was 20.9 IU/mL (multiple of the median [MOM] 0.83), hCG was 14.4 mIU/L (MOM 0.42) and her uE3 was 0.01 nmol/L (MOM 0.01). The extremely low uE3 indicated a possible placental sulfatase deficiency, congenital adrenal hypoplasia, or other unknown abnormality. On receiving this information, the obstetrician obtained a family history that was consistent with ichthyosis in the maternal grandfather and his siblings. Biochemical analysis of placenta documented the lack of sulfatase activity. This case illustrates that an extremely low level of maternal uE3 should prompt investigation of the family for evidence of X-linked ichthyosis associated with placental sulfatase deficiency.

Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome.

We investigated the role of vascular endothelial growth factor (VEGF) in ovarian hyperstimulation syndrome (OHSS). Two similar peaks of permeability activity were seen in OHSS ascites and liver ascites spiked with recombinant human VEGF (rhVEGF); no activity was seen in control liver ascites. Incubation with rhVEGF antiserum decreased activity in the two OHSS peaks by 79% and 65% and the two spiked liver peaks by 49% and 50%. Control serum produced 24% and 27%, and 17% and 0% reductions, respectively. This is evidence that the major capillary permeability agent in OHSS ascites fluid is VEGF.

Early and late presentation of the ovarian hyperstimulation syndrome: two distinct entities with different risk factors.

This study was designed to identify clinical predictors for early and late ovarian hyperstimulation syndrome (OHSS). A retrospective analysis of all 592 in-vitro fertilization (IVF) cycles from the programme's inception in 1988 up to March 1993 was performed. Six patients (1.0% of cycles) had moderate or severe OHSS presenting 3-7 days post-human chorionic gonadotrophin (HCG), and four patients (0.7% of cycles) had severe OHSS presenting 12-17 days post-HCG. No patient with early OHSS went on to develop late OHSS, and no patient with late OHSS had demonstrated early OHSS. Stepwise logistic regression showed that early OHSS was predicted by the number of oocytes retrieved (range 18-46) (P = 0.0001) and the oestradiol concentration on the day HCG was given (range 12,122-24,454 pmol/l) (P = 0.0003). Late OHSS was predicted by the number of gestational sacs (range 2-3) on ultrasound 4 weeks after embryo transfer (P = 0.0001) but not by the number of oocytes or oestradiol. Early OHSS was an acute effect of the HCG administered prior to egg retrieval in women with high oestradiol and larger numbers of follicles (range 22-51). Late OHSS was induced by the rising serum concentration of HCG produced by the early pregnancy, and in this series of cases it was associated only with multiple gestation.