Risk factors for cerebral palsy in neonates due to placental abruption.

AIM: This study aimed to identify risk factors for the onset of cerebral palsy (CP) in neonates due to placental abruption and investigate their characteristics. METHODS: A retrospective case-control study was conducted using a nationwide registry from Japan. The study population included pregnant women (n = 122) who delivered an infant with CP between 2009 and 2015, where placental abruption was identified as the single cause of CP. The control group consisted of pregnant women with placental abruption, who delivered an infant without CP and were managed from 2013 to 2014. They were randomly identified from the prenatal database of the Japan Society of Obstetrics and Gynecology (JSOG-DB; n = 1214). Risk factors were investigated using multivariate analysis. RESULTS: Alcohol consumption (3.38, 2.01-5.68) (odds ratio, 95% confidence interval), smoking during pregnancy (3.50, 1.32-9.25), number of deliveries (1.28, 1.05-1.56), polyhydramnios (5.60, 1.37-22.6), oral administration of ritodrine hydrochloride (2.09, 1.22-3.57) and hypertensive disorders in pregnancy (2.25, 1.27-4.07) were significant risk factors. In contrast, intravenous administration of oxytocin (odds ratio, 95% confidence interval: 0.22, 0.09-0.58) and magnesium sulfate (0.122, 0.02-0.89) attenuated risk. CONCLUSION: Alcohol consumption, smoking during pregnancy, number of deliveries, polyhydramnios, oral administration of ritodrine hydrochloride and hypertensive disorders in pregnancy were identified as risk factors for CP following placental abruption. Regarding alcohol consumption and smoking during pregnancy, the results suggest the importance of educational activities targeting pregnant women to increase their awareness of placental abruption.

Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13.

OBJECTIVE: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). STUDY DESIGN: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. RESULTS: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. CONCLUSION: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.

AMH Concentrations in Peritoneal Fluids of Women With and Without Endometriosis.

Background: As its name indicates, anti-Müllerian hormone (AMH) is primarily found as an inhibitor of the Müllerian duct in male fetus. On the other hand, AMH may act as a mediator of Müllerian duct-derived female tissue, such as endometrium in normal and pathological conditions. However, the role of AMH in the functional regulations of endometriosis is not well understood. It can be hypothesized that AMH in peritoneal fluids may affect the activity of peritoneal endometriosis. In this study, we investigated the levels of AMH in peritoneal fluids (PF) in women with and without endometriosis. Methods: PF were collected during laparoscopy from 90 women diagnosed as having advanced endometriosis (rASRM stage III, n = 30; stage IV, n = 60), and 32 women without endometriosis were served as control. Paired serum samples were also collected before the surgery. AMH in PF and serum were measured by ELISA. Individual clinical information was collected. AMH levels were compared according to the presence of endometriosis. The expression of AMHR2 in peritoneal endometriotic lesions obtained during laparoscopy was examined by immunohistochemistry. Results: AMH levels in PF were positively and significantly correlated with serum AMH levels in both women with and without endometriosis (R 2 = 0.17, P < 0.0001; R 2 = 0.30, P = 0.001, respectively). Serum AMH levels were inversely and significantly correlated with age in women with endometriosis (R 2 = 0.092, P = 0.004) and in control women without statistical significance (R 2 = 0.078, P = 0.12). AMH levels in PF were also inversely but not significantly correlated with age in women with and without endometriosis (R 2 = 0.029, P = 0.11 and R 2 = 0.027, P = 0.37, respectively). Mean age and serum AMH levels were not significantly different between two groups. On the other hand, AMH levels in PF were significantly lower in women with endometriosis compared to those of control women [2.15 ± 2.13 (mean ± SD) vs. 4.40 ± 4.77 ng/mL, P = 0.0001]. AMHR2 are localized at glandular epithelium and stromal cells in the ectopic endometrium of peritoneal endometriosis. Conclusions: Women with endometriosis may present lower PF AMH levels even if they retain serum levels similar to women without disease. As peritoneal endometriosis expresses a specific receptor for AMH, lower AMH levels in PF of women with advanced endometriosis may be involved in the pathophysiology of peritoneal endometriosis.

Ovarian reserve after three-step laparoscopic surgery for endometriomas utilizing dienogest: A pilot study.

PURPOSE: Surgery for endometriomas may cause detrimental effects on ovarian reserve. We evaluated the safety of three-step laparoscopic surgery for endometriomas utilizing dienogest in terms of post-surgical ovarian reserve. METHODS: Twelve women received first look laparoscopy (FLL) with fenestration and drainage. Immediately after the surgery, they took oral dienogest 2 mg for three months; then, they received second look laparoscopy (SLL) with cystectomy. We compared serum AMH levels between women had three-step management with dienogest, and another twelve women had conventional one-step surgery without medications. In women had three-step procedures, the changes in concentration of proinflammatory cytokines and chemokines in peritoneal fluids were evaluated. RESULTS: Serum AMH levels were significantly decreased after three months of dienogest following FLL. AMH levels were also significantly decreased 3-6 months both after SLL and after one-step surgery; however, recovery of serum AMH levels at 9-12 months after surgery was evident in women had three-step surgery comparing to those of one-step surgery. Proinflammatory cytokines and chemokines in peritoneal fluids were downregulated at the time of SLL comparing to those of FLL. CONCLUSIONS: Three-step surgery with dienogest may be a beneficial approach to protect ovarian reserve. Dienogest may exert its effects in part by lowering proinflammatory cytokines and chemokines.

Weekend and off-hour effects on the incidence of cerebral palsy: contribution of consolidated perinatal care.

OBJECTIVE: This study estimated the effects of weekend and off-hour childbirth and the size of perinatal medical care center on the incidence of cerebral palsy. METHODS: The cases were all children with severe cerebral palsy born in Japan from 2009 to 2012 whose data were stored at the Japan Obstetric Compensation System for Cerebral Palsy database, a nationally representative database. The inclusion criteria were the following: neonates born between January 2009 and December 2012 who had a birth weight of at least 2000 g and gestational age of at least 33 weeks and who had severe disability resulting from cerebral palsy independent of congenital causes or factors during the neonatal period or thereafter. Study participants were restricted to singletons and controls without report of death, scheduled cesarean section, or ambulance transportation. The controls were newborns, randomly selected by year and type of delivery (normal spontaneous delivery without cesarean section and emergency cesarean section) using a 1:10 case to control ratio sampled from the nationwide Japan Society of Obstetrics and Gynecology database. RESULTS: A total of 90 cerebral palsy cases and 900 controls having normal spontaneous delivery without cesarean section were selected, as were 92 cerebral palsy cases and 920 controls with emergent cesarean section. A significantly higher risk for cerebral palsy was found among cases that underwent emergent cesarean section on weekends (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.06-2.81) and during the night shift (OR 2.29, 95% CI 1.30-4.02). No significant risk was found among normal spontaneous deliveries on weekends (OR 1.63, 95% CI 0.97-2.73) or during the quasi-night shift (OR 1.26, 95% CI 0.70-2.27). Regional perinatal care centers showed significantly higher risk for cerebral palsy in both emergent cesarean section (OR 2.35, 95% CI 1.47-3.77) and normal spontaneous delivery (OR 2.92, 95% CI 1.76-4.84). CONCLUSION: Labor on weekends, during the night shift, and at regional perinatal medical care centers was associated with significantly elevated risk for cerebral palsy in emergency cesarean section.

Establishment of a novel diagnostic test algorithm for human T-cell leukemia virus type 1 infection with line immunoassay replacement of western blotting: a collaborative study for performance evaluation of diagnostic assays in Japan.

BACKGROUND: The reliable diagnosis of human T-cell leukemia virus type 1 (HTLV-1) infection is important, particularly as it can be vertically transmitted by breast feeding mothers to their infants. However, current diagnosis in Japan requires a confirmatory western blot (WB) test after screening/primary testing for HTLV-1 antibodies, but this test often gives indeterminate results. Thus, this collaborative study evaluated the reliability of diagnostic assays for HTLV-1 infection, including a WB-based one, along with line immunoassay (LIA) as an alternative to WB for confirmatory testing. RESULTS: Using peripheral blood samples from blood donors and pregnant women previously serologically screened and subjected to WB analysis, we analyzed the performances of 10 HTLV-1 antibody assay kits commercially available in Japan. No marked differences in the performances of eight of the screening kits were apparent. However, LIA determined most of the WB-indeterminate samples to be conclusively positive or negative (an 88.0% detection rate). When we also compared the sensitivity to HTLV-1 envelope gp21 with that of other antigens by LIA, the sensitivity to gp21 was the strongest. When we also compared the sensitivity to envelope gp46 by LIA with that of WB, LIA showed stronger sensitivity to gp46 than WB did. These findings indicate that LIA is an alternative confirmatory test to WB analysis without gp21. Therefore, we established a novel diagnostic test algorithm for HTLV-1 infection in Japan, including both the performance of a confirmatory test where LIA replaced WB on primary test-reactive samples and an additional decision based on a standardized nucleic acid detection step (polymerase chain reaction, PCR) on the confirmatory test-indeterminate samples. The final assessment of the clinical usefulness of this algorithm involved performing WB analysis, LIA, and/or PCR in parallel for confirmatory testing of known reactive samples serologically screened at clinical laboratories. Consequently, LIA followed by PCR (LIA/PCR), but neither WB/PCR nor PCR/LIA, was found to be the most reliable diagnostic algorithm. CONCLUSIONS: Because the above results show that our novel algorithm is clinically useful, we propose that it is recommended for solving the aforementioned WB-associated reliability issues and for providing a more rapid and precise diagnosis of HTLV-1 infection.

The Incidence of Dichorionic Diamniotic Twin Pregnancy After Single Blastocyst Embryo Transfer and Zygosity: 8 Years of Single-Center Experience.

Dichorionic diamniotic (DCDA) twin pregnancies after single blastocyst embryo transfer have been reported recently, although a blastocyst ovum is generally believed to divide into monochorionic twin pregnancy. We investigated the incidence of DCDA twin pregnancy after single blastocyst embryo transfer and their zygosity. This prospective cohort study included 655 consecutive twin pregnancies that were managed from 2006 to 2014 at our institution. Chorionicity and amnionicity were determined using first-trimester ultrasonography and/or placental pathology. Zygosity was analyzed if the cases were DCDA twins after single blastocyst embryo transfer. Among 655 twin pregnancies, there were 348 DCDA cases, 295 monochorionic diamniotic (MCDA) cases and 12 monochorionic monoamniotic cases. Single blastocyst embryo transfer was performed in 43 cases. Six out of the 43 (14%) cases involved DCDA twin pregnancies and the other 37 cases involved MCDA twin pregnancies. Three DCDA twins born after single blastocyst embryo transfer, wherein frozen embryo transfer (FET) was performed in the natural cycle, were dizygotic, and the other three cases, wherein FET with hormone replacement therapy was performed, were monozygotic. DCDA twin pregnancy occurred in 14% (7% for monozygotic and 7% for dizygotic) of twin pregnancies after single blastocyst embryo transfer cases.

Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing.

BACKGROUND: Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT. METHODS: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire. The qualitative data gathered from the questionnaire were analyzed using the N-Vivo software package. RESULTS: Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety, affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or termination, assuming the possibility that they were positive. CONCLUSIONS: Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women.

Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16INK4a Expression.

As p53-binding protein 1 (53BP1) localizes to the sites of DNA double-strand breaks and rapidly forms nuclear foci (NF), and its presence may be an indicator of endogenous genomic instability (GIN). We previously showed that 53BP1 NF in cervical cells increase with neoplastic progression, indicating the significance of 53BP1 expression for the estimation of malignant potential during cervical carcinogenesis. This study aimed to further elucidate the impact of 53BP1 expression as a biomarker for cervical squamous intraepithelial lesion (SIL). A total of 81 tissue samples, including 17 of normal cervical epithelium, 22 of cervical intraepithelial neoplasia (CIN) 1, 21 of CIN2, and 21 of CIN3, from patients positive for high-risk human papillomavirus (HR-HPV) were used for double-label immunofluorescence of 53BP1 and Ki-67/p16INK4a expression and HR-HPV in situ hybridization. We analyzed associations between 53BP1 expression type with parameters such as CIN grade, HR-HPV infection status, p16INK4a expression, and CIN prognosis. Expression type of 53BP1 was significantly associated with histological grade of CIN and HR-HPV in situ hybridization signal pattern (P < .0001). There was a significant correlation between 53BP1 and p16INK4a expression levels (r = .73, P < .0001). However, there was no association between 53BP1 expression type and CIN prognosis. We propose that 53BP1 expression type is a valuable biomarker for SIL, which can help estimate the grade and GIN of cervical lesions reflecting replication stress caused by the integration of HR-HPV to the host genome.

Impaired early-phase suppression of glucagon secretion after glucose load is associated with insulin requirement during pregnancy in gestational diabetes.

AIMS/INTRODUCTION: The role of glucagon abnormality has recently been reported in type 2 diabetes; however, its role in gestational diabetes mellitus (GDM) is still unknown. The glucose intolerance in GDM is heterogeneous, and not all patients require insulin treatment during pregnancy. Here, we investigated whether glucagon abnormality is associated with the requirement for insulin treatment during pregnancy. MATERIALS AND METHODS: A total of 49 pregnant women diagnosed with GDM were enrolled. They underwent a 75-g oral glucose tolerance test during mid-gestation, and we measured their plasma glucagon levels (by a new sandwich enzyme-linked immunosorbent assay) at fasting (0 min), and at 30, 60 and 120 min after glucose load in addition to the levels of plasma glucose and serum insulin. All participants underwent another oral glucose tolerance test at postpartum. RESULTS: Of the 49 patients, 15 required insulin treatment (Insulin group) and 34 were treated with diet therapy alone until delivery (Diet group). The early-phase glucagon secretion after glucose load, as determined by the changes in glucagon from the baseline to 30 min, was paradoxically augmented during mid-gestation in the Insulin group, but not in the Diet group. The impaired glucagon suppression during mid-gestation in the Insulin group was not associated with insulin secretory/sensitivity indexes studied, and was ameliorated postpartum, although the plasma glucose levels remained higher in the Insulin group versus the Diet group. CONCLUSIONS: Impaired early-phase suppression of glucagon could be associated with the requirement for insulin treatment during pregnancy in patients with GDM.

Comprehensive immune complexome analysis detects disease-specific immune complex antigens in seminal plasma and follicular fluids derived from infertile men and women.

BACKGROUND: Autoimmune reactions and subsequent inflammation may underlie spermatogenic dysfunction and endometriosis-related infertility. The aim of this study is to identify disease-specific antigens in immune complexes (ICs) in seminal plasma (SP) and in follicular fluid (FF). METHODS: Immune complexome analysis, in which nano-liquid chromatography-tandem mass spectrometry is employed to comprehensively identify antigens incorporated into ICs in biological fluids, was performed for specimens collected from infertile couples undergoing assisted reproduction. Forty-two male patients consisting of subjects with oligozoospermia (n = 6), asthenozoospermia (n = 8), and normal semen analysis (n = 28). Fifty-eight female patients consisting of subjects with ovarian endometriosis (n = 10) and control women without disease (n = 48). RESULTS: Four disease-specific antigens were identified in subjects with oligozoospermia, while five disease-specific antigens were detected in subjects with asthenozoospermia, some of which are involved in sprematogenesis. Eight antigens were detected only in subjects with endometriosis. CONCLUSION: Functional characteristics of disease-specific antigens were found to correspond to the pathogenesis of male and female infertility. The formation of ICs may contribute to spermatogenic dysfunction and endometriosis-related infertility via loss of function of the related proteins. Immune complexome analysis is expected to be a valuable tool for the investigation of novel diagnostic methods and treatment strategies for infertility.

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT.

OBJECTIVE: To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS: A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS: Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (<4%), and 18 (16.4%) cases including those with a maternal malignancy, were found to have altered genomic profile. Approximately half of the cases with nonreportable results had borderline z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%-33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection. CONCLUSIONS: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.

Correction: Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan.

Since the publication of this paper, the authors noticed that Yosuke Fujii was assigned to the incorrect affiliation. The affiliation information is provided correctly, above.

Fetal cell-free DNA fraction in maternal plasma for the prediction of hypertensive disorders of pregnancy.

OBJECTIVE: The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). STUDY DESIGN: This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed. RESULTS: A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP. CONCLUSION: A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult.

Reference values for circulating pregnancy-associated microRNAs in maternal plasma and their clinical usefulness in uncomplicated pregnancy and hypertensive disorder of pregnancy.

AIM: The aim of this study was to establish the reference values for circulating pregnancy-associated placental microRNAs in maternal plasma and clarify their clinical significance in patients with hypertensive disorder of pregnancy (HDP). METHODS: Blood samples were collected from 145 women with uncomplicated pregnancies (24, 26, 31 and 32 women at 12, 23, 30 and 36 weeks of gestation, respectively, and 32 women 1 day after delivery). Plasma concentrations of pregnancy-associated placental microRNAs (miR-515-3p, miR-517a, miR-517c and miR-518b) were measured by quantitative real-time reverse-transcription polymerase chain reaction. Reference values for each microRNA were determined by the line of best fit and 95% prediction interval and are expressed as logarithmic transformation. To clarify the clinical significance of these reference values, we measured the plasma concentrations of pregnancy-associated microRNAs in a different population comprising 33 pregnant women with HDP and 44 women with uncomplicated pregnancies. RESULTS: Reference values for circulating pregnancy-associated placental microRNAs on chromosome 19 miRNA clusters showed an increasing tendency as pregnancy progressed and decreased significantly 1 day after delivery (P < 0.05). The sensitivity and specificity of each reference value were 57.6% and 93.2% for miR-515-3p, 63.6% and 75.0% for miR-517a, 75.8% and 79.5% for miR-517c and 63.6% and 75.0% for miR-518b, respectively. The positive and negative predictive values of each reference value were 86.4% and 74.5% for miR-515-3p, 65.6% and 73.3% for miR-517a, 73.5% and 81.4% for miR-517c and 65.6% and 73.3% for miR-518b, respectively. CONCLUSION: Establishing the reference values for circulating pregnancy-associated placental microRNAs in maternal plasma could be useful for the evaluation of HDP.

Natural Course of Human T-Cell Leukemia Virus Type 1 Proviral DNA Levels in Carriers During Pregnancy.

The measurement of human T-cell leukemia virus type 1 (HTLV-1) proviral DNA levels by using polymerase chain reaction has been beneficial for confirming HTLV-1 infection during pregnancy. However, the influence of pregnancy on HTLV-1 infection and proviral DNA levels among pregnant women with HTLV-1 has not been clarified. We prospectively gathered blood samples from 36 pregnant women in whom HTLV-1 carriage was previously diagnosed and sequentially measured their proviral DNA levels. The HTLV-1 proviral DNA levels remained at a plateau during pregnancy but were elevated after delivery. Moreover, flow cytometry and serological analyses revealed that the regulatory T-cell population and soluble interleukin 2 receptor levels were similarly elevated after birth in comparison with those in control pregnant women. This study is the first to provide data on sequential changes in HTLV-1 proviral DNA levels during and after pregnancy. These findings will guide the establishment of a better program to prevent mother-to-child transmission of HTLV-1.

Relevant obstetric factors associated with fetal heart rate monitoring for cerebral palsy in pregnant women with hypertensive disorder of pregnancy.

AIM: The study identifies the relevant obstetric factors associated with fetal heart rate (FHR) monitoring for cerebral palsy (CP) in pregnant women with hypertensive disorders of pregnancy (HDP). METHODS: The subjects were neonates with CP (birth weight ≥ 2000 g, gestational age ≥ 33 weeks) who were approved for compensation for CP by the Operating Organization of the Japan Obstetric Compensation System between 2009 and 2012. After selection of women with antepartum HDP, obstetric characteristics associated with FHR monitoring were analyzed. RESULTS: The subjects included 33 neonates with CP whose mothers suffered from HDP during pregnancy and 450 neonates whose mothers did not develop HDP. The rates of placental abruption (48.5% vs. 20%; P < 0.001) and light-for-gestational age (12.1% vs. 2.2%; P = 0.011) were significantly higher in women with HDP than in those without HDP. Regarding FHR pattern analysis, fetal bradycardia was observed on admission to hospital in 94% of women with placental abruption. In women without placental abruption, FHR was likely to indicate a favorable pattern on admission, but became worse with the progression of labor. CONCLUSION: This is first study to clinically demonstrate FHR patterns in CP cases in association with HDP. Although antepartum CP is undetectable, pregnant women with HDP should be placed under strict observation and management to minimize fetal hypoxic conditions during labor.

Two consecutive successful live birth in woman with 17α hydroxylase deficiency by frozen-thaw embryo transfer under hormone replacement endometrium preparation.

17α-Hydroxylase deficiency is rare autosomal recessive disorder that manifested by hypertension, hypokalemia, delayed sexual development, primary amenorrhea and infertility. The information regarding infertility care and conception in women with this disorder are extremely limited. We report a 24-year-old Japanese woman with primary amenorrhea who was diagnosed as partial 17α-hydroxylase deficiency caused by homozygous 3 bp deletion in exon 1 of 17α-hydroxylase gene. In vitro fertilization with controlled ovarian stimulation was carried out and all viable embryo were frozen. During ovarian stimulation, serum progesterone levels were markedly elevated, and endometrial growth was impaired. Utilizing frozen-thaw embryo transfer under hormonal replacement (glucocorticoid, estradiol and progesterone), she had successfully given two consecutive live birth. Women with 17α-hydroxylase deficiency with residual ovarian reserve can afford reproductive success by appropriate diagnosis and treatment by assisted reproductive technology.

Association between ovarian endometrioma and ovarian reserve.

Endometrioma is one of the main pathologies of endometriosis, though its pathogenesis still remains enigmatic. Ovarian reserve is defined as the number and quality of the follicles left in the ovary at any given time. The cause of infertility in women with endometriosis is multifactorial. Diminished ovarian reserve is major concern in women with endometriosis-associated infertility. Cystectomy for endometriomas could negatively impact on post-operative ovarian reserve. Some women had surgery for endometriomas suffer from poor ovarian response, which directly affects treatment results. In addition, endometriomas themselves may be a cause of diminished ovarian reserve. Destruction of normal histological structure in ovarian cortex may affect dormancy of primordial follicles. Therefore, determination of ovarian reserve may serve as an important role in the management of reproductive health of women with endometriosis. Although the knowledge on the physiology of follicular development and mechanism of maintenance of ovarian reserve are rapidly accumulating, results obtained by ovarian reserve testing after surgery should be carefully evaluated according to the time-points and selected test. Further investigation on this issue is warranted.