Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF.

BACKGROUND: A biochemical marker for embryo development would increase the chance of a successful pregnancy with IVF by optimizing oocyte and embryo selection, and allow fewer embryos to be transferred. In this study, we correlated cumulus granulosa cell gene expression of hyaluronic acid synthase 2 (HAS2), cyclooxygenase 2 (COX2; PTGS2) and gremlin (GREM1) with subsequent embryo development in search of a parameter for embryo selection. METHODS: Cumulus cell gene expression was determined prospectively on eight consecutive patients undergoing IVF with ICSI. Immediately following oocyte retrieval, the cumulus was stripped from the oocyte, and cumulus gene expression for PTGS2, HAS2 and GREM1 was assessed using a one-step real-time quantitative RT-PCR assay. Oocyte quality, fertilization and embryo morphology were correlated to relative gene expression. RESULTS: Gene expression data were available on cumulus cells from 108 oocytes that developed into 70 embryos (64.8% fertilization rate). Cumulus PTGS2, HAS2 and GREM1 expression was higher from oocytes that developed into higher quality embryos (grades 3, 4 and 5) compared with lower quality embryos (grades 1 and 2) (P<0.05, P<0.001 and P<0.001, respectively). HAS2 and GREM1 expression was also higher from the cumulus surrounding oocytes that gave rise to higher grade embryos (P<0.001). The expression of PTGS2 and HAS2 was 6-fold higher, and that of GREM1 was 15-fold higher in cumulus yielding higher grade embryos versus lower grade embryos. CONCLUSION: PTGS2, HAS2 and GREM1 gene expression correlates to morphological and physiological characteristics and provides a novel approach to predict human embryo development. Ultimately, with better predictors of follicular and embryonic health, higher quality embryos can be selected and transferred, reducing higher order pregnancy rates.

Preimplantation genetic diagnosis for a known cryptic translocation: follow-up clinical report and implication of segregation products.

This report describes preimplantation genetic diagnosis (PGD) of a couple with a known paternally-derived balanced cryptic translocation 46,XY.ish t(2q;17q)(210E14-,B37c1+;B37c1-,210E14+) in embryos from a couple who previously had a child with severe mental retardation and was previously described in this journal [Bacino et al., 2000]. This child inherited the unbalanced product of translocation from her father: 46,XX.ish der(2)t(2q;17q)pat(210E14-,B37c1+). The couple desired a normal offspring and sought PGD to avoid clinical pregnancy termination. They were treated three times with in vitro fertilization followed by PGD. Two sequential FISH hybridizations were performed. In the first hybridization, telomeric probes to 2q and 17q and a chromosome 17 centromere probe were employed. The second hybridization screened for maternal age-related aneuploidy (X,Y,13,18,21). Of the 18 informative embryos, only 4 (22%) were normal. The remaining 12 (67%) were abnormal; most with unbalanced products (10/12) from the paternally-derived rearrangement. The most frequent mode of segregation observed for this cryptic translocation was adjacent-1 (7/18, 39%). This suggests cryptic translocations are amenable to PGD and, as are traditional translocations, demonstrate higher frequencies of unbalanced segregants than the empiric risk of 10-15% observed at amniocentesis or chorionic villus sampling. Thus, cryptic translocations presumably behave like overt translocations, in that PGD must be performed on a relatively large number of embryos to assure even 2-3 transferable embryos.

Current issues in medical management of ectopic pregnancy.

This review focuses on current medical therapy for unruptured ectopic pregnancy. Recently emerging issues include early diagnosis, treatment costs, intratubal methotrexate injection, medical treatment of cervical and interstitial ectopic pregnancies, and future fertility potential after methotrexate therapy. In addition, new clinical practice guidelines identify optimal candidates for medical therapy.

Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series.

In patients with poor response to ovarian stimulation with gonadotrophins, growth hormone (GH) is sometimes used to increase paracrine insulin-like growth factor-1 (IGF-1) effect. We postulated that dehydroepiandrosterone (DHEA) administration to poor responders would augment gonado-trophin effect via a similar mechanism. Baseline ovarian stimulation response to a cycle with DHEA in five healthy non-smoking women <41 years old was compared with day 3 FSH <20 mIU/ml. All had documented poor response to vigorous gonadotrophin administration. After day 2 ultrasounds, DHEA-sulphate (DHEA-S), FSH, human chorionic gonadotrophin (HCG), and testosterone were measured, and the women were given 80 mg/day of oral micronized DHEA for 2 months. While still on DHEA, they underwent ovarian stimulation with FSH given i.m. twice a day, and HCG (10 000 IU) at follicular maturity, followed by intrauterine insemination. Cycle parameters assessed were peak oestradiol, and peak oestradiol/ampoule. The DHEA/ovarian stimulation cycles occurred between 4 and 24 months after the control cycles. After 2 months DHEA treatment, DHEA-S increased to 544 +/- 55 microg/dl, and testosterone increased to 67.3 +/- 6.1 ng/dl. All five subjects (six cycles; one subject had two DHEA cycles) had increased responsiveness; peak oestradiol concentrations increased from 266.3 +/- 69.4 pg/ml to 939.8 +/- 418.9 pg/ml. The oestradiol/ampoule ratio increased in all six cycles, by a mean of 2.94 +/- 0.50 fold (P = 0.012). One of the cycles resulted in a delivered twin pregnancy. In this small series, DHEA improved response to ovarian stimulation even after controlling for gonadotrophin dose. Supplemental DHEA treatment during ovarian stimulation may represent a novel way to maximize ovarian response.

Transdermal testosterone treatment in women with impaired sexual function after oophorectomy.

BACKGROUND: The ovaries provide approximately half the circulating testosterone in premenopausal women. After bilateral oophorectomy, many women report impaired sexual functioning despite estrogen replacement. We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause. METHODS: Seventy-five women, 31 to 56 years old, who had undergone oophorectomy and hysterectomy received conjugated equine estrogens (at least 0.625 mg per day orally) and, in random order, placebo, 150 microg of testosterone, and 300 microg of testosterone per day transdermally for 12 weeks each. Outcome measures included scores on the Brief Index of Sexual Functioning for Women, the Psychological General Well-Being Index, and a sexual-function diary completed over the telephone. RESULTS: The mean (+/-SD) serum free testosterone concentration increased from 1.2+/-0.8 pg per milliliter (4.2+/-2.8 pmol per liter) during placebo treatment to 3.9+/-2.4 pg per milliliter (13.5+/-8.3 pmol per liter) and 5.9+/-4.8 pg per milliliter (20.5+/-16.6 pmol per liter) during treatment with 150 and 300 microg of testosterone per day, respectively (normal range, 1.3 to 6.8 pg per milliliter [4.5 to 23.6 pmol per liter]). Despite an appreciable placebo response, the higher testosterone dose resulted in further increases in scores for frequency of sexual activity and pleasure-orgasm in the Brief index of Sexual Functioning for Women (P=0.03 for both comparisons with placebo). At the higher dose the percentages of women who had sexual fantasies, masturbated, or engaged in sexual intercourse at least once a week increased two to three times from base line. The positive-well-being, depressed-mood, and composite scores of the Psychological General Well-Being Index also improved at the higher dose (P=0.04, P=0.03, and P=0.04, respectively, for the comparison with placebo), but the scores on the telephone-based diary did not increase significantly. CONCLUSIONS: In women who have undergone oophorectomy and hysterectomy, transdermal testosterone improves sexual function and psychological well-being.

Fertilization after standard in vitro fertilization versus intracytoplasmic sperm injection in subfertile males using sibling oocytes.

OBJECTIVE: To compare conventional IVF with ICSI in the subfertile male population using sibling oocytes. Results from males with isolated severe teratozoospermia also are analyzed. DESIGN: Prospective experimental study. SETTING: University based IVF clinic. PATIENT(S): Group A: 18 patients with one or more abnormalities in count, motility, or morphology. Group B: 20 patients with isolated severe teratozoospermia (< or = 4% Kruger Strict Criteria). INTERVENTION(S): Ovulation induction, random allocation of sibling oocytes, and IVF or ICSI. MAIN OUTCOME MEASURE(S): Fertilization rates (fertilization per cycle, fertilization per oocytes, and fertilization per couple) and embryo quality. RESULT(S): In group A, fertilization occurred in 13 of 18 (72%) of IVF cycles and 17 of 18 (94%) of ICSI cycles. Overall, 69 of 120 (58%) oocytes fertilized after IVF, whereas 80 of 131 (61%) fertilized after ICSI. The mean (+/-SEM) percent of oocytes fertilized per couple was 44.6%+/-9.0% with IVF and 62.7%+/-5.6% with ICSI (not statistically significant). In group B, fertilization occurred in 18 of 20 (90%) cycles after IVF and 20 of 20 (100%) cycles with ICSI. Overall, 54 of 113 (48%) of the oocytes fertilized after IVF, whereas 82 of 124 (66%) fertilized with ICSI. The mean (+/-SEM) percent of oocytes fertilized per couple was 50.9%+/-7.1 % with IVF and 66.6%+/-4.7% with ICSI. No statistically significant difference in embryo quality after IVF versus ICSI was demonstrated. CONCLUSION(S): With severe teratozoospermia, ICSI results in higher fertilization rates than conventional IVF, without altering embryo quality. In our subfertile male population, there is a trend toward improved fertilization with ICSI, with less failed fertilization.

Individual growth patterns in the first trimester: evidence for difference in embryonic and fetal growth rates.

OBJECTIVE: To evaluate individual fetal growth during the first trimester in pregnancies resulting from spontaneous and in vitro fertilization (IVF). METHODS: The growth of 11 fetuses conceived by spontaneous fertilization (known dates of ovulation) in nine patients and 15 fetuses conceived by IVF in 12 patients were evaluated at weekly intervals from 6 weeks, menstrual age, to 14 weeks. Fetal length was determined at each examination. Measures of fetal length included the crown-rump length (CRL), maximum straight line length (MSLL) and maximum axial length (MAL). Comparisons of CRL and MSLL to MAL were carried out. The MSLL was used as the measure of length except when the MAL was available. Linear and quadratic functions were fitted to the complete data sets of individual fetuses in the two groups. Individual data sets from ten fetuses in each group were then divided into early and late growth phases, and linear functions were fitted to each data subset. Start points and pivotal points for each fetus were estimated from the coefficients of these two functions. Growth in these two groups of fetuses was compared, on the basis of slope values. RESULTS: Evaluation of length measures indicated that, before 8 weeks, only MSLL could be measured. After 8 weeks, all three measures could be obtained, with the MAL being the largest. Both the linear and quadratic models performed well with individual data sets (mean R2(+/- SD): linear 98.1 (1.0)%; quadratic 99.4 (0.4)%), with no differences found between spontaneous and IVF groups (maximum possible differences in mean slopes (95% probability): 5-8%). Similar findings were obtained for the early and late growth phase data subsets. Slope values in the early and late growth phases showed low variability (CV: early 13.5%; late 11.6%), but were significantly different (early 0.72 (+/- 0.10 SD) cm/week; late 1.21 (+/- 0.14 SD) cm/week). The mean start point was 5.9 (+/- 0.3 SD) weeks' menstrual age, while the mean pivotal point was 9.2 (+/- 0.7 SD) weeks, menstrual age. CONCLUSIONS: First-trimester growth studies in individual fetuses indicate that there is a change in length growth rate between 9 and 10 weeks, menstrual age. This is consistent with a shift in development from organogenesis to growth. These results can be used for more accurate assessment of first-trimester growth and may aid in the detection of fetal problems that manifest themselves as growth abnormalities.

Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network.

BACKGROUND: Induction of superovulation with gonadotropins and intrauterine insemination are frequently used to treat infertility. We conducted a large, randomized, controlled clinical trial of these treatments. METHODS: We studied 932 couples in which the woman had no identifiable infertility factor and the man had motile sperm. The couples were randomly assigned to receive intracervical insemination, intrauterine insemination, superovulation and intracervical insemination, or superovulation and intrauterine insemination. Treatment continued for four cycles unless pregnancy was achieved. RESULTS: The 231 couples in the group treated with superovulation and intrauterine insemination had a higher rate of pregnancy (33 percent) than the 234 couples in the intrauterine-insemination group (18 percent), the 234 couples in the group treated with superovulation and intracervical insemination (19 percent), or the 233 couples in the intracervical-insemination group (10 percent). Stratified, discrete-time Cox proportional-hazards analysis showed that the couples in the group treated with superovulation and intrauterine insemination were 3.2 times as likely to become pregnant as those in the intracervical-insemination group (95 percent confidence interval, 2.0 to 5.3) and 1.7 times as likely as those in the intrauterine-insemination group (95 percent confidence interval, 1.2 to 2.6). The couples in the intrauterine-insemination group and in the group treated with superovulation and intracervical insemination were nearly twice as likely to conceive as those in the intracervical-insemination group. CONCLUSIONS: Among infertile couples, treatment with induction of superovulation and intrauterine insemination is three times as likely to result in pregnancy as is intracervical insemination and twice as likely to result in pregnancy as is treatment with either superovulation and intracervical insemination or intrauterine insemination alone.

Changes in adrenocortical function with aging and therapeutic implications.

Throughout life, the adrenal cortex exhibits dramatic morphogenic and steroidogenic changes. While there is subtle senescent decline in aldosterone, and a similarly subtle increase in cortisol, the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) decline with age in a situation similar to menopause, and this decline is considered by some to aggravate some age-related diseases. This decline is associated with an almost complete loss of the inner zone of the adrenal cortex, known as the zona reticularis. This review addresses these adrenal cortical changes, and explores their clinical significance. In particular, the clinical data on DHEA replacement in aging is addressed.

Testosterone delivery systems for women: present status and future promise.

In women, testosterone (T) is increasingly recognized as a steroid with multiple non-reproductive effects. Testosterone deficiency in menopausal women is more common than appreciated, particularly in patients on hormone replacement or with surgical menopause. Replacement of T is an established therapy for male hypogonadism, and as a result innovative new delivery systems have evolved to optimize physiologic delivery. However, in women, modalities of T replacement remain underdeveloped and at present provide artificial and/or supraphysiologic androgen levels. This review discusses the androgen replacement modalities presently available for women, and those being developed for future use.

Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-I and decreases high-density lipoprotein: a six-month trial.

OBJECTIVE: To determine the effect of administering 6 months of oral postmenopausal DHEA therapy on serum DHEA, DHEAS, and T levels and on physiologic endpoints including lipoproteins and insulin-like growth factor-I (IGF-I). DESIGN: Randomized, double-blind, parallel trial. SETTING: Academic referral practice. PATIENT(S): Thirteen normal-weight or overweight, healthy, nonsmoking, postmenopausal women. INTERVENTION(S): Administration of oral micronized DHEA (25 mg/d). MAIN OUTCOME MEASURE(S): Monthly fasting 23 hours postdose levels of serum DHEA, DHEAS, T, lipoproteins, IGF-I, IGF binding protein-3 (IGFBP-3), and liver function tests. Morphometric indices by dual-energy x-ray absorptiometry scan (percent body fat; lean body mass), immune indices, and insulin sensitivity. RESULT(S): Levels of DHEA, DHEAS, and T all rose into premenopausal ranges, but after 6 months, levels of DHEA and T did not differ from baseline or placebo. At 3 months, the ratio of IGF-I to IGFBP-3 rose by 36.1% +/- 12.7%, but it fell to placebo values by 6 months. High-density lipoprotein and apolipoprotein A1 levels declined. CONCLUSION(S): Patients appeared to tolerate 6 months of DHEA therapy well. Given the small study size, no statistically significant differences in morphometric indices, immune indices, or insulin-sensitizing properties were observed, but significant attenuation of bioavailability occurred. Supplementation with DHEA increased IGF-I/IGFBP-3 levels at 3 months and decreased high-density lipoprotein and apolipoprotein A1 levels at 6 months.

Heterotopic abdominal pregnancy treated at laparoscopy.

OBJECTIVE: To report a case of laparoscopic treatment of a heterotopic primary abdominal pregnancy after IVF with preservation of the concurrent intrauterine pregnancy. DESIGN: Case report. SETTING: University-based IVF program. PATIENT(S): A woman with a heterotopic abdominal pregnancy after IVF-ET. INTERVENTION(S): Pituitary down-regulation with luteal leuprolide acetate, ovulation induction with menotropins, IVF-ET, progesterone in oil for luteal support, laparoscopy, and resection of the abdominal gestation. MAIN OUTCOME MEASURE(S): Human chorionic gonadotropin levels, pelvic ultrasound examinations, and laparoscopic and pathologic findings. RESULT(S): A heterotopic abdominal pregnancy occurred after IVF-ET and was treated successfully with laparoscopy. The concurrent intrauterine pregnancy was delivered at term. CONCLUSION(S): Early diagnosis of an ectopic abdominal pregnancy allowed successful laparoscopic treatment, without sequelae to the intrauterine gestation.

Effect of postmenopausal estrogen replacement on circulating androgens.

OBJECTIVE: To determine the effect of estrogen replacement therapy (ERT) on serum androgen levels in postmenopausal women. METHODS: We measured serum dehydroepiandrosterone (DHEA), DHEA-sulfate, testosterone, estradiol (E2), LH, FSH, and sex hormone binding globulin in 8:00 AM fasting serum samples from a previous randomized, blinded, placebo-controlled crossover study in which 28 postmenopausal women (27 naturally menopausal) were given 2 mg/day of oral micronized estradiol. The treatment arms were 12 weeks with a 6-week washout. RESULTS: Estrogen replacement therapy raised mean (+/- standard error of the mean [SEM]) serum E2 from 8.7 +/- 1.0 to 117 +/- 18.7 pg/mL (P < .001 from baseline). Concurrently, mean (+/- SEM) DHEA-sulfate fell from 67.3 +/- 9.6 to 52.1 +/- 6.4 micrograms/dL (P < .001), and mean (+/- SEM) testosterone fell from 16.1 +/- 2.4 to 9.4 +/- 1.4 ng/dL (P = .006). Both FSH and LH declined significantly. Sex hormone binding globulin increased by 160% with ERT (P < .001). CONCLUSION: Menopausal ERT decreases serum androgen levels, decreasing DHEA-sulfate and testosterone by 23% and 42%, respectively. Whereas the decline in testosterone is likely due to decreased LH-driven ovarian stromal steroidogenesis, the declining levels of DHEA-sulfate also may imply a direct adrenal effect of estrogen. Bioavailable testosterone likely is reduced even more profoundly because sex hormone binding globulin is increased 160% by estrogen. Thus, menopausal ERT may induce relative ovarian and adrenal androgen deficiency, creating a rationale for concurrent physiologic androgen replacement.

Effect of sexual abstinence on the proportion of X-bearing sperm as assessed by multicolor fluorescent in situ hybridization.

OBJECTIVE: To document the relation between sexual abstinence and the proportion of X-bearing sperm in the ejaculate. DESIGN: Prospective cohort study. SETTING: Medical college. PATIENT(S): Ten normospermic men, aged 30 to 40 years, provided two semen samples: the first sample was obtained 1.0 to 1.5 days after ejaculation; the second, 7 to 10 days after ejaculation. INTERVENTION(S): Abstinence. MAIN OUTCOME MEASURE(S): Proportion of X- and Y-bearing sperm in two ejaculates. RESULT(S): Multicolor fluorescent in situ hybridization using directly labeled alpha-satellite probes specific for chromosomes 18, X and Y were used to analyze 40,273 sperm. After 1.0 to 1.5 days of abstinence, there were 47.6% +/- 1.7% (mean +/- SD) X-bearing sperm, and after 7 to 10 days of abstinence, there were 49.6% +/- 2.1% X-bearing sperm. The X:Y ratio increased marginally from 0.905 to 0.981. CONCLUSION(S): Sexual abstinence marginally increases the proportion of X-bearing sperm in the ejaculate as assessed by multicolor fluorescent in situ hybridization. This change of borderline statistical significance probably has little impact on the secondary sex ratio.

Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells.

Insulin and the insulin-like growth factors (IGFs) have multiple role in gene expression in steroidogenic cells. We investigated the regulation of steroidogenic enzyme gene expression by insulin and IGF-I in primary cultures of human adrenocortical cells from donors of ages 19-77 years. The effects of insulin and IGF-I observed here were independent of age and sex of the donor. After 5 days in serum-containing medium, cultures were exposed to insulin or IGF-I together with cyclic AMP analogs or ACTH in serum-free defined medium. Insulin and IGF-I at physiological concentrations increased mRNA levels for 17 alpha-hydroxylase and type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in the absence of cyclic AMP or ACTH. They had lesser effects on 21-hydroxylase and cholesterol side-chain cleavage enzyme mRNA levels and were3 without effect on 11 beta-hydroxylase mRNA. All steroidogenic enzyme mRNAs were strongly increased by cyclic AMP or ACTH, and this increase was potentiated by insulin or IGF-I. These effects of insulin and IGF-I were accompanied by decreases in the ratio of dehydroepiandrosterone/cortisol synthesized from pregnenolone by the cultures. Induction of steroidogenic enzyme genes in adult human adrenocortical cells by insulin and IGF-I is unlikely to occur by means of a cyclic AMP-dependent mechanism. These data increase the evidence for an important regulation of steroidogenesis by these hormones.

The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3 beta-hydroxysteroid dehydrogenase.

Based on indirect evidence, it has often been assumed that the zona reticularis of the adult human adrenal cortex is the source of the adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), but direct tests of this concept have been few. Using the techniques of cell culture, Northern blotting, and RIA, we compared the properties of separated adult zonal cells to those of fetal zone cells, a cell type well known to secrete large amounts of DHEA(S) due to its low expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). In nine glands from donors of a wide age range, the zona fasciculata and zona reticularis were separated and dissociated, and the cells were placed in culture. After 5 days, serum was removed by a 24-h period in serum-free defined medium followed by a 24-h exposure to cAMP analogs, with the optional addition of insulin, also in serum-free medium. The separated fasciculata and reticularis cells showed large differences in the DHEA(S)/cortisol (F) production ratios from added pregnenolone precursor, consistent with the synthesis of only F and essentially no DHEA(S) by fasciculata cells and with the synthesis of mostly DHEA(S) with little or no F by both reticularis cells and fetal zone cells. The different patterns of steroidogenesis were accompanied by a much lower level of expression of type II 3 beta HSD in reticularis cells, similar to that in fetal zone cells. In contrast, other genes were similarly regulated in the two adult zones and in the fetal zone by both cAMP and insulin. The levels of messenger ribonucleic acids for 17 alpha-hydroxylase, cholesterol side-chain cleavage enzyme, 21-hydroxylase, and 11 beta-hydroxylase responded to cAMP and insulin in both reticularis cells and fetal zone cells in the same pattern as that previously established in fasciculata cells. The central role of the limited expression of 3 beta HSD in the DHEA(S)-synthesizing property of reticularis cells was established by inhibition of 3 beta HSD in fasciculata cells with trilostane, which caused them to increase their DHEA/F production ratio to a level exceeding even that in fetal zone cells. There did not appear to any age-related changes in gene expression that could account for the large age-related decline in DHEA(S) biosynthesis in humans in either reticularis or fasciculata cells. Thus, the most likely cause of the age-related decline in adrenal androgen biosynthesis is an age-related decline in the number of functional reticularis cells, without a major change in the differentiated properties of the zonal cells as a function of age.

Single serum progesterone as a screen for ectopic pregnancy: exchanging specificity and sensitivity to obtain optimal test performance.

OBJECTIVE: To investigate the diagnostic accuracy of screening serum P in diagnosis of ectopic pregnancy (EP) and to identify a cutoff value that provides the best compromise between test sensitivity and specificity. DESIGN: Retrospective analysis. SETTING: University hospital. INTERVENTIONS: Observation only. PATIENTS: First trimester pregnant women at risk for EP. MAIN OUTCOME MEASURE: Single P measurements were obtained from 3,674 pregnancies with outcomes defined as EP, viable intrauterine pregnancy (IUP), and spontaneous abortion (SAB). Diagnostic accuracy of the test was analyzed by generating receiver operating characteristic (ROC) curves, which quantify the ability of the test to distinguish EP and SAB from IUP. RESULTS: Diagnostic accuracy for EP versus IUP was 88.7% +/- 0.1% (mean +/- SEM); for SAB versus IUP, 93.8% +/- 0.4%; and for SAB + EP versus IUP, 92.8% +/- 0.4%. Diagnostic accuracy for SAB versus EP was only 39.4% +/- 0.2%. In the interval of 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L), P missed 5.3% of the EPs and incorrectly included 84.3% of the viable IUPs; in the interval of 20.0 to 24.9 ng/mL (63.6 to 79.2 nmol/L), sensitivity improved in that only 3.5% of the EPs were missed but 88.8% of viable IUPs were included incorrectly. A cutoff value of > or = 17.5 ng/mL (55.7 nmol/L), the median point of the 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L) interval, missed only 35 of 423 (8.3%) total EPs in the study. CONCLUSION: Analysis of ROC curves demonstrates that single serum P has high diagnostic accuracy for differentiating accidents of pregnancy (SAB and EP) from viable IUP, both individually (SAB versus IUP and EP versus IUP) and collectively (SAB + EP versus IUP); it cannot efficiently discriminate SAB versus EP. We conclude that for P > or = 17.5 ng/mL (55.7 nmol/L), patients thought to be at risk for EP may be followed reasonably without ultrasound or further invasive diagnostic studies.

Ovarian hyperstimulation augments adrenal dehydroepiandrosterone sulfate secretion.

OBJECTIVE: To determine if factor(s) secreted by the ovaries during hyperstimulation potentiate basal and ACTH-stimulated adrenal androgen secretion. DESIGN: Retrospective and prospective and prospective clinical study. SETTING: University tertiary care center infertility clinic. PARTICIPANTS: Two hundred thirteen hyperstimulation cycles in endocrinologically normal women were identified from 92 patients with ovulatory infertility, aged 25 to 45 years. Further, seven endocrinologically normal infertile women, aged 22 to 37 years, who were undergoing empiric ovarian hyperstimulation for infertility were identified and studied. INTERVENTIONS: In the previously performed cycles, basal and peak serum DHEAS and cortisol (F) levels were assayed and compared with each other and to the extant E2 levels. Additionally, at the baseline and the peak of ovarian hyperstimulation cycles, a standard ACTH test was performed and serum was assayed for DHEAS, DHEA, and F. MAIN OUTCOME MEASURE: Basal and ACTH-stimulated serum DHEAS, DHEA (prospective part only), and F concentrations. Where applicable, mean peak values were generated and compared between the baseline and the peak of stimulation with or without a correction for intrapatient variability in F secretion. RESULTS: Basal serum DHEAS levels rose with ovarian hyperstimulation independent of F. Post-ACTH mean peak value concentrations rose with ovarian hyperstimulation for DHEAS but not DHEA or F. CONCLUSIONS: Ovarian hyperstimulation potentiates basal and ACTH perturbed adrenal DHEAS secretion. This implies the existence of a humoral ovarian factor(s) that mediate this ovarian-adrenal cross-talk.