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Biomedical subjects

R V Haning

Publications and source records attributed to R V Haning.

At least 19 recordsLinked to original sources

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.

Abortion, Spontaneous

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.

Female

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.

Chorionic Gonadotropin

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.

Chorionic Gonadotropin

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).

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

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.

Adult

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.

Adult

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.

Adult

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.

Animals

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.

Chorionic Gonadotropin

Dehydroepiandrosterone sulfate and anovulation increase serum inhibin and affect follicular function during administration of gonadotropins.

To test the hypothesis that testosterone (T) derived from circulating dehydroepiandrosterone sulfate (DS) or produced in excess within the anovulatory ovary is a follicular regulator capable of stimulating inhibin secretion. DS and inhibin were determined by RIA in residual serum samples from in vitro fertilization cycles and analyzed along with other parameters using analysis of variance and stepwise multiple linear regression after log transformation of the RIA data. It was predicted that the serum concentration of inhibin would be higher in women with anovulation than in normal subjects and that the serum inhibin concentration would have a positive regression coefficient on the serum DS concentration. The serum concentrations of inhibin (P < 0.01) and estradiol (P < 0.001) on the day of hCG treatment were higher in women with anovulation than in normal subjects, as was the number of oocytes retrieved (P < 0.001). The FSH and LH doses (both P < 0.005) and age (P < 0.001) were significantly lower, and the average duration of gonadotropin therapy was 1 day shorter (P < 0.001) in anovulatory patients. There was no significant difference in serum DS (P > 0.2). Regression analysis showed that serum inhibin was positively related to the number of oocytes (P < 0.001) and serum DS (P = 0.05), with an increase in anovulatory subjects (P < 0.025). The duration of treatment with gonadotropins was related positively to the patient's age (P < 0.001) and negatively to serum DS (P < 0.025), with a decrease in anovulatory subjects (P < 0.025). The number of oocytes obtained was negatively related to age (P < 0.001) and positively to serum DS (P < 0.005). These data are consistent with a stimulatory effect of follicular T derived from either circulating DS or the anovulatory ovary, which affects the secretion of inhibin, the duration of gonadotropin treatment, and the number of oocytes retrieved.

Adult

Proliferative index of human luteinized granulosa cells varies as a function of ovarian reserve.

OBJECTIVE: We examined whether the proliferative index of luteinized granulosa cells, as determined by flow cytometry, varied as a function of a woman's ovarian reserve, as reserve, as reflected by follicular-phase day 3 serum follicle-stimulating hormone. STUDY DESIGN: This prospective cohort study consisted of 19 women of similar chronologic age preparing for in vitro fertilization-embryo who met specific day 3 serum follicle-stimulating hormone criteria. The "low follicle-stimulating hormone" group consisted of 11 women with day 3 serum follicle-stimulating hormone levels < or = 6 IU/L. The "high follicle-stimulating hormone" group consisted of eight women with day 3 serum follicle-stimulating hormone levels > or = 18 IU/L. A total of 56 preovulatory follicles containing > or = 10(4) luteinized granulosa cells were examined by flow cytometry. The low follicle-stimulating hormone group was compared with the high follicle-stimulating hormone group to examine proliferative index as a function of serum day 3 follicle-stimulating hormone levels. RESULTS: The low follicle-stimulating hormone group had a greater proliferative index (11.1% +/- 0.4%) than did the high follicle-stimulating hormone group (8.3% +/- 0.6%), p < 0.001). This study demonstrates that in spite of the same chronologic age, luteinized granulosa cells from preovulatory follicles of women with day 3 serum follicle-stimulating hormone levels > or = 18 IU/L have a 25% decreased proliferative index compared with luteinized granulosa cells from women with day 3 serum follicle-stimulating hormone levels < or = 6. CONCLUSIONS: This suggests that granulosa cell proliferation is influenced by ovarian reserve and may explain in part the more favorable response to ovulation induction protocols that younger women demonstrate compared with women of more advanced reproductive age.

Adult

Gonadotropin-releasing hormone agonist-induced differences in granulosa cell cycle kinetics are associated with alterations in follicular fluid müllerian-inhibiting substance and androgen content.

We have previously shown that the proliferative index (PI), as determined by flow cytometry of luteinized granulosa cells obtained at oocyte retrieval, is greater in ovulation induction regimens which include the GnRH analog (GnRH-a) leuprolide acetate than those using human menopausal gonadotropin (hMG) only. Specific growth factors or intrafollicular hormones may contribute to this leuprolide acetate-induced difference in cell cycle kinetics. We examined whether differences in the PI of these granulosa cells are associated with the alterations of follicular fluid content of Mullerian-inhibiting substance (MIS) and other intrafollicular hormones including FSH, estradiol, progesterone, androstenedione, and testosterone. The control group consisted of follicular fluid obtained from 18 follicles from 4 women receiving hMG alone. The GnRH-a treated group consisted of follicular fluids obtained from 55 follicles aspirated from 18 women receiving GnRH-a in addition to hMG. One-way analysis of variance using log-transformed data and expressed as geometric means with 95% confidence intervals, demonstrated that the follicles from the control group had a significant 14-fold higher concentration of 2.46 ng/mL MIS, 95% CI (1.8-4.8) vs. 0.18 ng/mL, 95% CI (0.13-0.24) P < 0.0005, a 3-fold higher concentration of 17.55 nmol/L androstenedione, 95% CI (14.6-20.9) vs. 5.76 nmol/L, 95% CI (3.1-10.5) P < 0.02, and a 1.5-fold higher concentration of 29.43 nmol/L testosterone 95% CI (22.5-38.14) vs. 19.3 nmol/L, 95% of CI (11.1-33.9) P < 0.01 than GnRH-a treated follicles, although the PI value in controls was half that of the GnRH-a group. These data demonstrate that GnRH-a induced differences in granulosa cell cycle kinetics are associated with alterations of MIS and androgen intrafollicular fluid content and suggest that MIS may be a mitotic inhibitor of human granulosa cells.

Adult

Plasma dehydroepiandrosterone sulfate serves as a prehormone for 48% of follicular fluid testosterone during treatment with menotropins.

Evidence has suggested that dehydroepiandrosterone sulfate (DS) is a prehormone for ovarian steroidogenesis. To study this hypothesis, combined 6-h infusions of [3H]dehydroepiandrosterone sulfate and [14C]testosterone ([14C]T) were performed in four normal women treated with menotropins who were undergoing medically indicated surgery, and the data were compared to those from nine normal women. The concentrations of tracer and nonisotopic DS, androst-5-ene-3 beta,17 beta-diol sulfate (delta 5diolS), androst-5-ene-3 beta,17 beta-diol (delta 5diol), dehydroepiandrosterone (D), androstenedione (delta 4A), and T were determined in arterial and venous blood and in follicular fluid. From these data, the concentrations and fractions of steroids in the follicular fluid that were derived from DS were calculated from the specific activity of intravascular DS and the concentrations of follicular fluid tracer steroids and their specific activities. The fractions of T (0.48), delta 5diol (0.31), delta 5diolS (0.42), and D (0.25) in follicular fluid arising from circulating DS were similar and were not significantly different from that of follicular DS arising from circulating DS (0.32). However, the fraction of follicular fluid delta 4A (0.041) was significantly less (P < 0.01), and the fractions of intrafollicular estrone and estradiol arising from DS were both less than 0.04. The mean MCR of DS in the women treated with menotropins of 22.0 +/- 3.5 L/day (mean +/- SE) was significantly higher than the normal control value. These findings elucidate an important mechanism of adrenal/ovarian interaction at the level of steroidogenesis; circulating DS serves as a prehormone for the production of intrafollicular delta 5diolS, delta 5 diol, D, and T.

Adult

Testosterone, a follicular regulator: key to anovulation.

To study the interrelationships of steroids within the follicle, combined 6-h infusions of [3H]dehydroepiandrosterone sulfate and [14C] testosterone ([14C]T) were performed in four normal women treated with menotropins who were undergoing medically indicated surgery. The concentrations of tracer and/or nonisotopic dehydroepiandrosterone sulfate, androst-5-ene-3 beta,17 beta-diol sulfate, androst-5-ene-3 beta,17 beta-diol, dehydroepiandrosterone, androstenedione, T, dihydrotestosterone, estrone (E1), and estradiol (E2) were determined in arterial and venous blood and follicular fluid. The log-transformed product/precursor ratio of [3H]dihydrotestosterone/[3H]T in follicular fluid was negatively correlated with the log-transformed follicular concentrations of E1 (P = 0.01) and E2 (P = 0.02), suggesting a reciprocal relationship between 5 alpha-reductase and follicular E1 and E2. E2 and T were positively correlated in follicular fluid (r = 0.84; P = 0.0003), suggesting a stimulatory action of follicular T on aromatase. These findings along with extensive published data suggest that follicular T functions as a follicular regulator, enhancing follicular aromatase activity when adequate amounts of FSH are available. These conclusions have important implications with regard to mechanisms for selecting the dominant follicle and producing atresia in the remaining cohort of follicles, and they describe a final common path in the pathophysiology of anovulation.

Anovulation

Steroid sulfatase in the human ovary and placenta: enzyme kinetics and phosphate inhibition.

In 5 placental homogenates the Km of steroid sulfatase for DHEA sulfate increased from 15.4 in Tris buffer to 26.8 microM in phosphate (both buffers 0.1 M, pH 7.4), P less than 0.05. In 3 pooled ovarian preparations the Km increased from 14.3 microM in Tris to 33.0 microM in phosphate, P less than 0.01. There was no significant difference between the ovarian and placental values for Km in either Tris or phosphate (P greater than 0.5), and the increase in the Km produced by phosphate in ovarian tissue was not significantly different from that in the placenta (P greater than 0.5). In the placentas the Vmax in Tris was 1420 pmol/min/mg protein and this fell to 523 pmol/min/mg protein in phosphate (P less than 0.005). The Vmax was 50-fold higher in the placenta than in the ovary in either Tris or phosphate (both P less than 0.001). In the ovary, the Vmax was 27.6 pmol/min/mg protein in Tris and 11.0 pmol/min/mg protein in phosphate (P less than 0.05). The reduction of Vmax produced by phosphate in the ovary was not significantly different from that in the placenta (P greater than 0.5). The slope of the 1/v vs 1/S plot (Km/Vmax) increased 4.7-fold in the placentas and 5.8-fold in the ovaries in phosphate over that in Tris (both P less than 0.001); the increase in the placentas was not significantly different from that in the ovaries (P greater than 0.5). Phosphate ion acts as a mixed inhibitor of both placental and ovarian steroid sulfatase.

Arylsulfatases

Luteal phase support and severe ovarian hyperstimulation syndrome.

The incidence and statistical associations of the ovarian hyperstimulation syndrome (OHSS) were studied in 304 egg retrievals with gonadotrophin-releasing hormone agonist suppression, gonadotrophin administration and follicular aspiration. In addition to preserving corpus luteum function, the luteal phase administration of human chorionic gonadotrophin (HCG) was associated with a higher incidence of severe OHSS than was supplementation with progesterone alone (12 versus 0%, P less than 0.001). Severe OHSS occurred in 3.7% and 12% of retrievals without and with pregnancy respectively (P less than 0.01). Stepwise logistic regression showed that the occurrence of moderate or severe OHSS was statistically predicted by the log of the serum oestradiol on the day the initial HCG was given (P less than 0.0001), treatment with luteal phase HCG (P less than 0.0003), and fetal number (P less than 0.0079). In the late luteal phase of cycles without luteal HCG, the serum oestradiol concentration was one-tenth and the serum progesterone concentration was one-fifth of the luteal phase value with HCG support (P less than 0.001). Without luteal phase HCG, oestradiol was two-fold higher (P less than 0.001) and progesterone was 1.4-fold higher (P less than 0.005) in pregnant than in non-pregnant women. With luteal phase HCG, oestradiol was 1.4-fold higher in pregnant than in non-pregnant women (P less than 0.05), and progesterone was 1.7-fold higher (P less than 0.001). Oestradiol upper limits of 4400 and 14,700 pmol/l (1200 and 4000 pg/ml) for cycles with and without luteal phase HCG respectively correspond to approximately 5% risk of moderate or severe OHSS with a singleton pregnancy under these conditions.

Chorionic Gonadotropin

Metabolic clearance rate of dehydroepiandrosterone sulfate, its metabolism to testosterone, and its intrafollicular metabolism to dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone in vivo.

At the time of surgery, women were infused with [3H]dehydroepiandrosterone sulfate ([3H]DS)/[14C]testosterone ([14C]T) for 6 h; blood samples were obtained from an artery the ovarian veins, and a peripheral vein; and fluid was obtained from ovarian follicles. Both blood and follicular fluid samples were analyzed for radioactivity as DS, dehydroepiandrosterone (D), androstenedione (delta 4A). T, and dihydrotestosterone (DHT), and the blood was also analyzed for the concentration of nonisotopic DS by RIA. In other subjects the concentrations of D and DS were measured in paired samples of blood and follicular fluid. From these data, values of 13.6 +/- 0.69 L/day four (mean +/- SE; n = 4) for MCRDS, 607 +/- 90 L/day (n = 3) for MCRT, and 0.0190 +/- 0.0089 (n = 3) for [p]DS-T (fraction of plasma DS metabolized to plasma T) were obtained. The ratio of the concentration of the tracer-labeled steroid in the follicular fluid to the concentration in the arterial plasma sample was elevated significantly above 1 for three 3H-labeled and three [14C-labeled metabolites: [3H]D (21-fold; P less than 0.001), [3H]T (81-fold; P less than 0.001), [3H]DHT (19-fold; P less than 0.001), [14C]T (4-fold; P less than 0.025), [14C]DHT (21-fold; P less than 0.01), and [14C]delta 4A (50-fold; P less than 0.001). The estimated concentrations of steroids in follicular fluid derived from DS based on specific activity calculations were as follows: [geometric mean (95% confidence limits; n)]: DS, 5600 (4800-6500 nmol/L; 12); D, 370 (88-1500 nmol/L; 10); delta 4 A, 120 (67-220 nmol/L; 12); T, 130 (39-450 nmol/L; 10); and DHT, 64 (35-120 nmol/L; 8). Comparison of these data to known follicular fluid steroid concentrations shows that DS from the intravascular pool can be used as an ovarian prehormone.

Adult