Live birth rate with double ovarian stimulation is superior to follicular phase ovarian stimulation per started cycle in poor ovarian responders.

AIM: To compare the outcome of double ovarian stimulation (DOS) with follicular phase ovarian stimulation (FPS) per started cycle in poor ovarian responders (PORs). METHODS: A total of 204 PORs who underwent ovulation induction for in vitro fertilization, cryopreservation of all embryos available, and frozen embryo transfer cycle were retrospectively analyzed. Of those, 146 received single FPS, and 58 received DOS. All viable embryos were cryopreserved and subsequently transferred within 1-6 months. RESULTS: The number of oocytes collected and the number of mature oocytes per started cycle were higher in the DOS group compared to the FPS group (6.0 ± 1.9 vs. 2.8 ± 1.3 and 4.3 ± 1.3 vs. 2.2 ± 1.2, respectively, p = 0.001). Clinical pregnancy rate and live birth rate per started cycle were also significantly higher in the DOS group than the FPS group (41.4% vs. 16.4% and 36.2% vs. 15.1%, respectively, p < 0.001). The cancellation rate of embryo transfer due to no viable embryo was significantly lower in the DOS group (10.3%) than the FPS group (40.4%) (p = 0.001). In the DOS group, numbers of oocytes (3.2 ± 1.2 vs. 2.7 ± 1.1, p = 0.006), MII oocytes (2.6 ± 1.0 vs. 2.1 ± 0.8, p = 0.001), and cryopreserved blastocysts (1.5 ± 0.8 vs. 1.1 ± 0.7, p = 0.002) were significantly higher in the luteal ovarian stimulation compared to follicular ovarian stimulation. CONCLUSIONS: Live birth per started cycle with DOS is superior to FPS in PORs. Luteal phase stimulation contributes to improving pregnancy rates in these patients.

Investigation of Physiological Effects Induced by Dehydroepiandrosterone in Human Endothelial Cells and Ovarian Cancer Cell Line

Objectives: Dehydroepiandrosterone (DHEA) is an endogenous hormone that acts as a ligand for several cellular receptors. An age-dependent decline in circulating levels of DHEA is linked to changes in various physiological functions. In gynecological clinical practice, DHEA is commonly prescribed to induce ovulation. Some clinical studies report a positive association between high serum concentrations of DHEA and an increased risk of developing ovarian cancer. However, the in vitro physiological effects of DHEA on ovarian cancerous cells have not been explored thus far. In this study, we aimed to investigate the physiological effects of DHEA treatment (0-200 µM, 24-72 hours) on MDAH-2774 human ovarian cancer cell line and primary HuVeC human endothelial cells. Materials and Methods: The physiological effects of DHEA treatment (0-200 µM, 24-72 hours) on MDAH-2774 human ovarian cancer cell line and primary HuVeC human endothelial cells were investigated with the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test, acridine orange/ethidium bromide staining, and scratch assay. Results: DHEA treatment promoted proliferation of the MDAH-2774 cancer cell line in a dose-dependent manner (r=0.6906, p<0.0001, for 24 hours) (r=0.6802, p<0.0001, for 48 hours) (r=0.7969, p<0.0001, for 72 hours). In contrast, DHEA inhibited proliferation of the primary HuVeC cells (r=0.9490, p<0.0001, for 24 hours) (r=0.9533, p<0.0001, for 48 hours) (r=0.9584, p<0.0001, for 72 hours). In agreement with these observations, DHEA treatment resulted in a dose-dependent increase in the number of necrotic cells in the primary HuVeC cells (r=0.97, p<0.0001). However, the number of necrotic or apoptotic cells did not change significantly when the MDAH-2774 cells was exposed to DHEA. Moreover, we found that DHEA treatment reduced the migration rate of HuVeC cells in a dose-dependent manner (r=0.9868, p<0.0001), whereas only a slight increase was observed in the MDAH-2774 ovarian cancer cell line (r=0.8938, p<0.05). Conclusion: Our findings suggest that DHEA promotes the proliferation of ovarian cancer cells in a dose-dependent manner in vitro. Moreover, DHEA induced necrosis and inhibited proliferation in endothelial cells. Although mechanistic evidence is required, our preliminary findings imply that exposure to high doses of DHEA may be associated with an increased risk of developing ovarian cancer.

Serum vitamin D levels in healthy urban population at reproductive age: effects of age, gender and season.

OBJECTIVE: The aim of the study was to determine the effects of age, gender and season on vitamin D status in healthy urban population at reproductive age. Also, we investigated the distribution of population into different groups regarding 25(OH)D levels. METHODS: Serum 25(OH)D levels of 21,317 participants: 5,364 men (25.1%) and 15,953 women (74.8%), aged between 18-45 years, applying to two medical centres for check-up located in the same city were retrospectively analyzed. Group I consisted of 14,720 participants (11,257 women and 3,463 men) in the first centre and Group II consisted of 6,597 participants (4,696 women and 1,901 men) in the second centre. RESULTS: The mean 25(OH)D levels did not differ between women and men in both groups: 23.4 (SD = 14.4) and 23.1 (SD = 12.6) in Group I, and 22.6 (SD = 15.9) and 23.1 (SD = 14.3) in Group II, respectively, (p > 0.05). Similar trends exhibiting lower mean 25(OH)D levels at younger ages and higher levels at later ages were observed in both groups; a seasonal variation of 25(OH)D levels was observed in both genders with the highest levels in August and September and the lowest levels from February through April; percentages of women with 25(OH)D level of < 5 ng/ml were significantly higher than of men in Group I (1.4% vs. 0.2%, respectively, p < 0.001) and in Group II (4.1% vs. 1.1%, respectively, p < 0.001). CONCLUSION: There is a slight increase in serum 25(OH)D levels from 18 through 45 years of age in healthy population. The seasonal variation of 25(OH)D levels is prominent in both genders with men having slightly lower levels in some months of winter and higher levels in summer as compared to women. The prevalence of women having 25(OH)D levels less than 5 ng/ml is higher than that of men.

Metformin decreases testicular damages following ischaemia/reperfusion injury in rats.

The effects of metformin on a testicular torsion injury in adolescent rat testis after I/R were evaluated in the present study. Forty adolescent rats were divided into five groups with eight rats per group: a control group; a sham-operated group; an ischaemia group, where torsion was applied for 4 hr and testis was examined immediately after detorsion; an I/R group, where torsion was applied for 4 hr and the testis was examined 4 hr after detorsion; and an I/R + M group, where the metformin (300 mg/kg) administration was added to the identical procedures used for the I/R group. Spermatogenesis, basal membrane integrity and cleaved caspase-3 expression were assessed. The I/R + M group had a significantly higher Johnsen score than the I/R group (7.9 ± 0.1 vs. 7.5 ± 0.2; p < .001; F-value = 14.2). Failure of basal membrane integrity was highest in the ischaemia group (45 ± 5) compared to the other groups (control group, 20 ± 5; sham-operated group, 16.6 ± 2.8), but not different between the I/R + M (31.6 ± 12.5) and the I/R groups (25 ± 3.5). Cleaved caspase-3 expression was highest in the ischaemia group (73.5 ± 0.7), and significantly lower in the I/R + M group (33.4 ± 0.9) than the I/R group (58.5 ± 0.2; p < .05; F-value = 7.6). Metformin decreases testicular damage by exerting protection against the harmful effects of I/R on spermatogenesis and alleviating apoptosis in adolescent rat testis.

Doxorubicin-induced testicular damage is related to PARP-1 signaling molecules in mice.

BACKGROUND: Doxorubicin (DOX), is a chemotherapeutic agent, which evokes oxidative stress and cell apoptosis in testicular tissue. It is known that the activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP), leading to apoptosis induced by DOX. The aim of the present study is to investigate whether PARP pathway has a role in DOX-induced testicular damage and infertility utilizing pharmacological PARP-1 inhibitor, PJ34, and PARP-1 knockout mice model. METHODS: Firstly, we assessed the activation of PARP pathway after DOX-induction at various hours by immunohistochemistry and western blot analysis. Secondly, we evaluated the role of PARP pathway in DOX-induced testicular damage, sperm motility, and fertility with pharmacological inhibition of PARP by using PJ34. Finally, we aimed to correlate a functional relationship between PARP-1 and DOX using PARP-1 knockout mice in DOX-induced testicular damage. Doxorubicin levels in plasma and testis tissue were also assessed. RESULTS: In DOX-induced group; PARP-1, PAR and apoptotic pathway protein expressions, increased significantly. In DOX + PJ34 group; PAR, cytochrome c, and AIF levels decreased significantly. Testicular weights, sperm motility, and mean the number of pups per litter decreased in DOX-induced group after 28 days, however they were similar to the control group in DOX-PJ34 group. In PARP-1 KO group, seminiferous tubule morphology was impaired significantly after 28 days of DOX-administration. CONCLUSIONS: Our study indicates that DOX-induced testicular damage may be related to over-activation of PARP-1. PJ34 application was effective in preventing severe testicular damage caused by DOX-injection and may be considered for fertility protection against DOX-induced testicular damage.

Results of intracytoplasmic sperm injection performed with sperm retrieved by microscopic testicular sperm extraction in azoospermic patients.

OBJECTIVE: The absence of any sperm in the ejaculate is called azoospermia and it is detected in 1% of males and 10-15% of those with infertility complaints. Azoospermia may be due to obstructive (OA) and non-obstructive (NOA) causes. Today, healthy pregnancies can be achieved in azoospermic patients by intracytoplasmic sperm injection (ICSI) performed using sperm retrieved from microscopic testicular sperm extraction (m-TESE). In this study, we examined the sperm retrieval rates with m-TESE in azoospermic patients, the results of ICSI in OA and NOA patients with sperm and the underlying testicular pathologies in patients without sperm. MATERIAL AND METHODS: Patients who underwent m-TESE at IVF unit of our hospital between January 2005 and April 2017 were retrospectively reviewed. A total of 342 azoospermic patients (117 OA and 225 NOA cases) with regular follow-up were included in the study. In these cases, sperm retrieval and clinical pregnancy rates after ICSI were compared. RESULTS: In the m-TESE procedure, motile sperm was found in all of the OA patients and in 52.4% (118/225) of the NOA patients. Clinical pregnancy rate in the OA group was 29.9% (35/117) and live birth rate was 25.6% (30/117). In the NOA group, the clinical pregnancy rate was 27.1% (32/118) and the live birth rate was 23.7% (27/118). Histopathologic evaluation was made in 107 cases in the NOA group with no testicular sperm, revealing that 59 cases with germ-cell aplasia (sertoli-cell only syndrome), 42 cases with maturation arrest, and 6 cases with hypospermatogenesis. Postoperative hematoma developed in 3 of m-TESE cases and subsided with conservative treatment. CONCLUSION: If motile sperm is retrieved with m-TESE application in azoospermic patients, pregnancy resulting in one live birth in about 4 couples who undergo ICSI application can be achieved. In the presence of motile sperm, live birth rates are similar between OA and NOA case with very low complication rates.

Osteogenesis imperfecta Type IV: a newly identified variant at position c.560 (G > T; p.Gly187Val) in the COL1A2 gene.

Osteogenesis imperfecta is a clinically heterogenous disease caused by defective collagen syntesis associated with a mutation in the COL1A1 or COL1A2 genes. In this report, we present a case of osteogenesis imperfecta (OI) type IV, seen in a female fetus with incurved femurs at 18 weeks of gestation. Molecular analysis of the newborn revealed a novel mutation at position c.560 (c.560 G > T) of the exon 12 in the COL1A2 gene; which lead to the glycine modification with valine (p.Gly187Val) at codon 187. The pregnancy follow-up was uneventful. After delivery, the newborn underwent biphosponat therapy and no fracture was detected until 1 year old.

Gonadotropin-releasing hormone agonist triggering with concomitant administration of low doses of human chorionic gonadotropin or a freeze-all strategy in high responders.

OBJECTIVES: To compare the live birth rates and moderate/severe ovarian hyperstimulation syndrome (OHSS) rates of 2 different approaches using gonadotropin-releasing hormone (GnRH) agonist triggering in high responder women. Methods: A retrospective cohort study was performed to evaluate intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) outcomes in high responder women who underwent ovulation induction with a GnRH antagonist protocol between April 2011 and March 2015. In group 1 (n=74), GnRH agonist was used for ovulation triggering with the concomitant use of 1500 IU of urinary human chorionic gonadotropin (hCG) immediately after oocyte retrieval followed by fresh ET and standard luteal support. In group 2 (n=48), GnRH agonist was used for triggering after freezing all embryos and subsequent frozen/thawed embryo transfer (FET); this approach is considered the "freeze-all" approach. Results: Baseline characteristics were similar between the groups. The clinical pregnancy rates for group 1 was 45.9% and group 2 was 43.8% (p=0.812, chi-squared test) and live birth rates for group 1 was 40.5% and for group 2 41.7% (p=0.902, chi-squared test) were comparable between groups. In group 1, late-onset OHSS was observed (one severe case and one moderate case) in 2 patients (2.7%). In group 2, none of the patients experienced moderate/severe OHSS. Conclusion: The live birth rate with GnRH agonist triggering and concomitant use of 1500 IU of hCG immediately after oocyte retrieval was similar to that obtained with the freeze-all approach and FET in a subsequent cycle. The administration of a low dose of hCG in GnRH agonist trigger cycles caused moderate/severe OHSS in 2.7% of the patients.

Live birth rate with repeat microdissection TESE and intracytoplasmic sperm injection after a conventional testicular biopsy in men with nonobstructive azoospermia.

OBJECTIVE: To determine live birth rate via m-TESE and ICSI in men who had a previous conventional testicular biopsy. STUDY DESIGN: Retrospective study was conducted to analyze 86 m-TESE procedures for ICSI in NOA patients who had a previous conventional TESE. Only motile spermatozoa were used for ICSI and all other forms were discarded. Women under the age of 42 years and who produced at least 3 oocytes in response to controlled ovarian stimulation were included in the study. Statistical significance was tested using Student's t-test, χ(2) test and Fisher's exact test as appropriate. RESULTS: Testicular motile spermatozoa were successfully retrieved in 39 out of 47 men who had spermatozoa found in the previous biopsy (Group I), and in 6 out of 39 men with no sperm in the previous biopsy (Group II) (82.9% vs. 15.3%, respectively; p<0.01). Demographic characteristics of two groups were similar. Live birth rate per repeat m-TESE attempt via ICSI was significantly higher (23.4%, 39/47) in patients with a previous sperm-positive TESE compared to that (2.5%, 1/39) obtained in patients with a previous sperm-negative testicular biopsy (p<0.05). CONCLUSION: Repeat attempt to obtain motile spermatozoa by m-TESE following conventional TESE ensures a higher recovery and live birth rate in men who had spermatozoa found in the first recovery procedure compared to men with no spermatozoa in the first testicular biopsy. Live birth rate through ICSI is not promising after repeat m-TESE procedure in patients with a previous sperm-negative testicular biopsy.

The expression of HER-2/neu (c-erbB2), survivin and cycline D1 in serous ovarian neoplasms: their correlation with clinicopathological variables.

Ovarian cancer is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of HER-2/neu (c-erbB2), survivin and cycline D1 biomarkers in serous ovarian neoplasms and their correlations with clinicopathological variables in serous ovarian cancers. We analyzed pathological specimens of 62 patients with benign (n = 25), borderline (n = 14) and malignant (n = 23) serous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Significantly more immunoreactivity with HER-2/neu was detected in malignant tumors (100 %) compared to borderline (78.6 %) and benign tumors (48 %) (P < 0.01). Survivin expression was significantly higher in malignant tumors (91.3 %) than those found in borderline (71.4 %) and benign tumors (24 %) (P < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (95.6 %) compared to borderline (85.7 %) and benign tumors (48 %) (P < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant serous tumors. In terms of clinicopathological variables, only tumor grade was associated with the expression of all biomarkers others exhibited different correlations in serous ovarian cancers. The expressions of HER-2/neu (c-erbB2), survivin and cycline D1 are positively correlated with the malignant potential of serous ovarian neoplasms.

Screening cytomegalovirus, rubella and toxoplasma infections in pregnant women with unknown pre-pregnancy serological status.

PURPOSE: To determine the prevalence of acute cytomegalovirus (CMV), rubella and T. gondii infections among pregnant women who had no serological status tested for these microorganisms prior to pregnancy in a metropolitan area. METHODS: A cross-sectional study was undertaken between January 2009 and January 2013 in 1,258 women presenting for their first antenatal visit (between 6 and 11 weeks of gestation). All women were tested for IgG and IgM antibodies. Subsequently, avidity test was utilized for inconclusive results. They were followed until delivery and all newborns were examined by a pediatrician. RESULTS: Presence of IgM antibody positivity alone was not detected in any women. Avidity test excluded primary infection in 15 out of 16 (93.7 %) women who were positive for both IgG and IgM antibodies. Amniocentesis was performed in one case with borderline IgG avidity for T. gondii. No primary infections were detected in any newborn for the infections screened. The prevalences of IgG antibodies were 95 % for rubella, 84.1 % for CMV and 23.1 % for T. gondii. CONCLUSIONS: Assessment of IgG and IgM antibodies followed by IgG avidity testing for inconclusive results may be an acceptable approach in pregnant women with unknown serological status prior to pregnancy. Utilization of IgG avidity as a supplemental test prevented unnecessary intervention in IgG and IgM antibodies positive patients. No primary infection was detected for CMV, rubella and T. gondii infections in the urban population screened.

Comparison of the transfer of equal numbers of blastocysts versus cleavage-stage embryos after repeated failure of in vitro fertilization cycles.

PURPOSE: To evaluate the efficacy of blastocyst transfer in women with at least two previously unsuccessful in vitro fertilization-embryo transfer (IVF-ET) attempts. METHODS: Retrospective analysis of 238 couples (with previous implantation failures) had equal number (two) of cleavage-stage embryos (n = 143) or blastocysts (n = 95) transferred in the same IVF center. RESULTS: The clinical pregnancy rates and live-birth rates were similar in the cleavage-stage embryo transfer group and the blastocyst group (35.6% vs. 40% and 32.1% vs. 35.7%; p > 0.05, respectively). Miscarriage rates (9.8% vs. 10.5%) and multiple pregnancy rates (15.6% vs. 23.6%) did not differ. Although implantation rate was higher with blastocyst transfer than that with day 3 transfer, it did not reach to a statistical significance (24.7% and 19%, respectively, p > 0.05). CONCLUSION: Blastocyst transfer in ICSI cycles does not yield a better outcome than that obtained with cleavage-stage embryos in women who had unsuccessful IVF attempts previously.

Effect of antithyroid antibodies on ICSI outcome in antiphospholipid antibody-negative euthyroid women.

Antithyroid antibodies (ATA) are found in 5-15% of women at reproductive age and are not necessarily accompanied with thyroid dysfunction. ATA are associated with adverse effects such as spontaneous miscarriage, recurrent miscarriages, preterm delivery and maternal post-partum thyroiditis in women with normal thyroid hormone concentrations. The role of ATA on the outcome of IVF cycles remains to be investigated. This study evaluated the impact of ATA on the outcome of intracytoplasmic sperm injection (ICSI)-embryo transfer cycles in euthyroid women. A total of 253 women undergoing ICSI-embryo transfer cycles were prospectively enrolled in this study. Women positive for at least one of the thyroid antibodies, with normal thyroid-stimulating hormone (TSH) and free T4 concentrations and negative for anticardiolipin antibodies and lupus anticoagulant were included. ICSI was performed for fertilization in all cycles. Of 253 women, 219 were ATA negative and 34 ATA positive. Implantation rates (19.1% versus 18.4%), miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy rates (37.0% versus 32.4%) did not differ significantly between the ATA-positive group and the ATA-negative group, respectively. The presence of antithyroid antibodies in euthyroid and antiphospholipid antibody-negative women was not found to significantly affect the outcome of ICSI-embryo transfer cycles. Antithyroid antibodies (ATA) can interact with thyroid hormone receptors located on the human oocyte and impair the chance of fertilization and healthy pregnancy. They are found in 5-15% of women at reproductive age and are not necessarily accompanied with thyroid dysfunction. ATA have been reported to be associated with adverse effects such as spontaneous miscarriage, recurrent miscarriages, preterm delivery and maternal post-partum thyroiditis in women with normal thyroid hormone concentrations. The role of ATA on the outcome of IVF cycles remains to be investigated. The objective of our study was to evaluate the impact of ATA on the outcome of intracytoplasmic sperm injection (ICSI)-embryo transfer cycles in euthyroid women. A total of 253 women undergoing ICSI-embryo transfer cycles were prospectively enrolled in this study. Women with at least one of the thyroid antibodies positive and normal TSH and free T4 concentrations were included in the study. Since other immunological disorders might affect the results, antiphospholipid antibodies (APA), which are the markers of antiphospholipid antibody syndrome, were also screened in all women prior to study. Women with positive for APA were excluded in the final analysis. Of 253 women, 219 (86.6%) were ATA negative and 34 (13.4%) ATA positive. Implantation rates (19.1% versus 18.4%), biochemical pregnancy rates (9.2% versus 14.3%), miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy rates (37.0% versus 32.4%) did not differ significantly between the ATA-positive group and the ATA-negative group, respectively. In conclusion, presence of antithyroid antibodies in euthyroid and antiphospholipid antibody-negative women does not affect the outcome of ICSI-embryo transfer cycles.

Outcome of intracytoplasmic sperm injection cycles with fresh testicular spermatozoa obtained on the day of or the day before oocyte collection and with cryopreserved testicular sperm in patients with azoospermia.

OBJECTIVE: To compare the outcome of intracytoplasmic sperm injection (ICSI)-ET cycles with fresh testicular spermatozoa obtained on the same day or the day before oocyte retrieval with frozen-thawed spermatozoa. DESIGN: Retrospective cohort study. SETTING: Fertility center. PATIENT(S): The first ICSI-ET cycle of 337 couples with motile testicular spermatozoa of azoospermic patients. INTERVENTION(S): Microdissection testicular sperm extraction (TESE), sperm cryopreservation, ICSI-ET. MAIN OUTCOME MEASURE(S): Fertilization, implantation, clinical pregnancy rates (PRs) and delivery rates. RESULT(S): Testicular sperm retrieval was performed on the day of oocyte retrieval in 166 cycles (group A), the day before oocyte retrieval in 42 cycles (group B), and the frozen-thawed testicular spermatozoa were used in 129 cycles (group C). The groups were comparable in terms of the ages of male and female patients, ovarian response to stimulation, as well as the number of oocytes injected. The number of cycles with nonobstructive azoospermia and obstructive azoospermia was evenly distributed in each group. Fertilization rates were 70.7%, 68.7%, and 67.3%, clinical PRs 31.3%, 30.9%, and 25.5%, and delivery rates 28.9%, 28.5%, and 23.2% for groups A, B, and C, respectively. The outcomes of patients with nonobstructive azoospermia did not differ from those of patients with obstructive azoospermia within and among the groups. CONCLUSION(S): Neither the timing of TESE (on the day of or the day before oocyte retrieval) nor the use of frozen-thawed testicular sperm affects the outcome of ICSI-ET cycle when motile spermatozoa are obtained in azoospermic men. In addition, etiology of azoospermia does not have any influence on the outcome with different timing of microdissection TESE procedure for ICSI.

11beta-Hydroxysteroid dehydrogenase activity in pregnancies complicated by hydatidiform mole.

PROBLEM: 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) plays an important role in regulating active glucocorticoid reaching the fetus. In normal pregnancy, placental 11beta-HSD functions primarily in oxidative direction. Placental tissue of patients with pregnancies complicated by pre-eclampsia exhibit significantly lower type 1 and 2 11beta-HSD activities and significantly high cortisol level in cord blood suggesting fetal exposure to higher level of active glucocorticoids. The activity of 11beta-HSD in gestational trophoblastic disease has not been determined. The objective of this study was to assess 11beta-HSD activity in tissue from normal second trimester and pregnancies complicated by hydatidiform mole. METHOD OF STUDY: Normal placental tissues were obtained from patients undergoing termination of pregnancy, and from patients undergoing uterine evacuation for hydatidiform mole. Both nicotinamide adenine dinucleotide (NAD)- and nicotinamide adenine dinucleotide phosphate (NADP)-dependent activities were assayed in central villous tissue. Comparison of groups was performed using Student's t-test. A P-value of 0.05 was considered significant. Data are presented as mean +/- S.D. RESULTS: Tissue obtained from five patients with pathology-proven hydatidiform mole demonstrated significantly lower 11beta-HSD activities compared with placental tissue obtained from normal pregnancies. The mean NAD-dependent 11beta-HSD activity in normal placentas was 386 +/- 109 pmol/min/g placenta and in hydatidiform mole was 74 +/- 54 pmol/min/g placenta (P < 0.01). The mean NADP-dependent 11beta-HSD activity in normal placentas was 370 +/- 120 pmol/min/g placenta and in trophoblastic disease was 68 +/- 69 pmol/min/g placenta (P < 0.01). CONCLUSION: Our data indicate significant impairment in the ability of hydatidiform mole tissue to inactivate glucocorticoids.