What is the impact of endometriosis and the AFS stage on cumulative pregnancy rates in IVF programs?

BACKGROUND: Endometriosis is commonly observed in infertile women and can be staged with regard to severity [e.g. according to the American Fertility Society (AFS) classification]. This condition can cause infertility through impaired oocyte quality, fertilization disorders, tubal lesions, adhesions, deep infiltration, and adenomyosis. Although women with endometriosis often turn to in vitro fertilization (IVF) programs, the literature data on IVF outcomes are sometimes contradictory (i.e. the same as in other etiologies of infertility, or worse). The objective of the present study was to assess and compare pregnancy rates in women with and without endometriosis and according to the endometriosis stage. METHODS: We retrospectively studied clinical and ongoing pregnancy rates in IVF and the cumulative pregnancy rates after frozen/thawed embryo transfers, in women without endometriosis (group A) or with endometriosis (group B). We further compared groups in which endometriosis was staged according to the revised AFS classification: stage 1/2 (group C), stage 3/4 (group D, without endometrioma), and endometrioma alone (group E). RESULTS: We documented 430 cycles in group A and 460 in group B (including 56 in group C, 88 in group D and 316 in group E). After fresh or frozen/thawed embryo transfers, the differences in ongoing pregnancy rates between groups A and B were not significant. However the cumulative rates per couple were significantly lower (p < 0.05) in group D. CONCLUSIONS: We recommend IVF for women with endometriosis because the pregnancy rates are similar to those observed for women with other types of infertility. This approach is in line with the international guidelines issued by assisted reproductive technology societies. These results again raise the question of whether surgical resection of deep infiltrating endometriosis (stage 3/4) should be recommended before admission to an IVF program. Trial registration This study was approved by an institutional review board (CPP Ouest VI, Brest, France): reference: B2020CE.43.

Family history of postpartum hemorrhage is a risk factor for postpartum hemorrhage after vaginal delivery: results from the French prospective multicenter Haemorrhages and Thromboembolic Venous Disease of the Postpartum cohort study.

BACKGROUND: Postpartum hemorrhage is a major component of perinatal morbidity and mortality that affects young women worldwide and is still often unpredictable. Reducing the incidence of postpartum hemorrhage is a major health issue and identifying women at risk for postpartum hemorrhage is a key element in preventing this complication. OBJECTIVE: This study aimed to estimate postpartum hemorrhage prevalence after vaginal delivery and to identify postpartum hemorrhage risk factors. STUDY DESIGN: Unselected pregnant women ≥16 years of age admitted to 1 of 6 maternity wards in Brittany (France) for vaginal birth after 15 weeks of gestation were recruited in this prospective, multicenter cohort study between June 1, 2015, and January 31, 2019. Postpartum hemorrhage was defined as blood loss ≥500 mL in the 24 hours following delivery. Independent risk factors for postpartum hemorrhage were determined using logistic regression. Missing data were imputed using the Multivariate Imputation by Chained Equations method. RESULTS: Among 16,382 included women, the postpartum hemorrhage prevalence was 5.37%. A first-degree family history of postpartum hemorrhage (adjusted odds ratio, 1.63; 95% confidence interval, 1.24-2.14) and a personal transfusion history (adjusted odds ratio, 1.90; 95% confidence interval, 1.23-2.92) were significantly associated with postpartum hemorrhage. The use of oxytocin during labor was also a risk factor for postpartum hemorrhage (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.44). Inversely, smoking during pregnancy and intrauterine growth restriction were associated with a reduced risk for postpartum hemorrhage (adjusted odds ratio, 0.76; 95% confidence interval, 0.63-0.91, and 0.34; 95% confidence interval, 0.13-0.87, respectively). CONCLUSION: In addition to classical risk factors, this study identified a family history of postpartum hemorrhage and personal transfusion history as new characteristics associated with postpartum hemorrhage after vaginal delivery. The association of postpartum hemorrhage with a family history of postpartum hemorrhage suggests a hereditary hemorrhagic phenotype and calls for genetic studies. Identifying women at risk for postpartum hemorrhage is a key element of being prepared for this complication.

An exceptional case of degenerative endometriosis of the uterine torus.

There are less than ten cases of deep endometriosis degeneration in the literature. The duration of endometriosis, the ovarian stimulation, the perimenopause and the obesity exposes the woman to an increased risk of endometriosis degeneration.

Venous Thromboembolism Associated with Assisted Reproductive Technology: A Systematic Review and Meta-analysis.

BACKGROUND: Hormonal exposure leads to an increased risk of venous thromboembolism (VTE) but the risk of VTE associated with assisted reproductive technology (ART) is not clearly determined. METHODS: We searched in PubMed, EMBASE, Web of Science, and the Cochrane Library databases and identified all relevant articles published up to February 1, 2021. The primary objective was to determine the frequency of VTE associated with ART. Secondary objectives were to determine (1) the risk of VTE associated with ART as compared to pregnancy without ART; (2) the risk of VTE associated with ovarian hyperstimulation syndrome (OHSS); and (3) to determine potential risk factors of VTE related to ART. RESULTS: Fourteen studies were included. The overall frequency of VTE associated with ART was 0.23% (95% confidence interval [CI]: 0.07-0.46). Women undergoing ART had a two- to threefold increased risk of VTE as compared to spontaneous pregnancy (relative risk [RR]: 2.66; 95% CI: 1.60-4.43). The overall frequency of VTE specifically related to OHSS was <0.001%. The risk of VTE after ART complicated by OHSS, as compared to ART without OHSS, was higher but not statistically significant (RR: 14.83; 95% CI: 0.86-255.62). Risk factors of VTE associated with ART were in vitro fertilization procedure (RR, odds ratio [OR], and hazard ratio varying from 1.77, 95% CI: 1.41-2.23 to 4.99, 95% CI: 1.24-20.05), hyperhomocysteinemia (OR: 15.2; 95% CI: 2.0-115.0), polycystic ovarian syndrome (PCOS) (RR: 4.8; 95% CI: 1.7-13.4), successful ART leading to pregnancy (OR: 13.94; 95% CI: 1.41-137.45). CONCLUSION: Further large prospective studies on risk factors of VTE in women undergoing ART are needed in order to optimize thromboprophylaxis in this context.

Live Birth Rates in Women Under 38 Years Old with AMH Level < 1.2 ng/ml in the First In Vitro Fertilization + / - Intracytoplasmic Sperm Injection: Retrospective Study and Arguments for Care.

Many studies failed to show a predictive impact of AMH levels on the chances of pregnancy; however, acceptable pregnancy rates for young women with low AMH levels were observed in IVF + / - ICSI. The objectives of this retrospective study were to evaluate the clinical pregnancy and live birth rates in the first IVF + / - ICSI cycle in women under 38 years old with AMH level < 1.2 ng/ml and to determine the arguments for care. We classified the women into three groups: group A: AMH < 0.4 ng/ml (n: 86); group B: AMH: 0.4 to 0.8 ng/ml (n: 90); and group C: AMH > 0.8 to < 1.2 ng/ml (n: 92). We recorded data on the patients' characteristics, stimulation cycles, embryo cultures, and ongoing pregnancies. No difference was observed between the three groups for the number of embryos transferred, the clinical pregnancy, and the live birth rates (LBR) per embryo transfer (LBR/transfer: 24.1% in group A, 25.9% in group B, and 28.1% in group C). The young age of the women reassures about the oocyte quality, but a low level of AMH may raise concerns about a lower quantitative oocyte yield, leading to accelerated management of the couple in IVF + / - ICSI.

High-Dose Supplementation of Folic Acid in Infertile Men Improves IVF-ICSI Outcomes: A Randomized Controlled Trial (FOLFIV Trial).

Dietary supplementation is commonly used in men with male infertility but its exact role is poorly understood. The aim of this multicenter, randomized, double-blind, placebo-controlled trial was to evaluate the impact of high-dose folic acid supplementation on IVF-ICSI outcomes. 162 couples with male infertility and an indication for IVF-ICSI were included for one IVF-ICSI cycle. Male partners of couples wishing to conceive, aged 18-60 years old, with at least one abnormal spermatic criterion were randomized in a 1:1 ratio to receive daily supplements containing 15 mg of folic acid or a placebo for 3 months from Day 0 until semen collection for IVF-ICSI. Sperm parameters and DNA fragmentation before and after the treatment and the biochemical and clinical pregnancy rates after the fresh embryo transfer were analyzed. We observed an increase in the biochemical pregnancy rate and a trend for a higher clinical pregnancy rate in the folic acid group compared to placebo (44.1% versus 22.4%, p = 0.01 and 35.6% versus 20.4%, p = 0.082, respectively). Even if no changes in sperm characteristics were observed, a decrease in DNA fragmentation in the folic acid group was noted (8.5 ± 4.5 vs. 6.4 ± 4.6, p < 0.0001). High-dose folic acid supplementation in men requiring IVF-ICSI for male infertility improves IVF-ICSI outcomes.

GREB1L variants in familial and sporadic hereditary urogenital adysplasia and Mayer-Rokitansky-Kuster-Hauser syndrome.

Congenital uterine anomalies (CUA) may have major impacts on the health and social well-being of affected individuals. Their expressivity is variable, with the most severe end of the spectrum being the absence of any fully or unilaterally developed uterus (aplastic uterus), which is a major feature in Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). So far, etiologies of CUA remain largely unknown. As reports of familial occurrences argue for strong genetic contributors in some cases, we performed whole exome sequencing in nine multiplex families with recurrence of uterine and kidney malformations, a condition called hereditary urogenital adysplasia. Heterozygous likely causative variants in the gene GREB1L were identified in four of these families, confirming GREB1L as an important gene for proper uterine and kidney development. The apparent mode of inheritance was autosomal dominant with incomplete penetrance. The four families included fetuses with uterovaginal aplasia and bilateral renal agenesis, highlighting the importance to investigate GREB1L in such phenotypes. Subsequent sequencing of the gene in a cohort of 68 individuals with MRKH syndrome or uterine malformation (mostly sporadic cases) identified six additional variants of unknown significance. We therefore conclude that heterozygous GREB1L variants contribute to MRKH syndrome and this probably requires additional genetic or environmental factors for full penetrance.

Scoring system avoids Chlamydia trachomatis overscreening in women seeking surgical abortions.

OBJECTIVE: To develop and validate a predictive score to avoid unnecessary screening and prophylactic antibiotic use in abortion clinics by identifying a group of women who are at very low risk for Chlamydia trachomatis (CT) infection. METHODS: This population-based retrospective study includes 1000 women who underwent surgical abortion between January and September 2010. The main outcome measure was the rate of CT infection among women seeking an induced abortion according to sociodemographic and clinical data. The score was developed by using two-thirds of the data set as the derivation sample to identify the strongest predictors of CT. A receiver operating characteristic curve established cutoffs and applied the score to the remaining one-third (validation sample). RESULTS: The rate of CT infection was 6.7%. Three criteria were independently associated with CT: gestation more than 10 weeks (adjusted odds ratio [aOR], 1.96; 95% confidence interval [95% CI], 1.06-3.64), not using contraception (aOR, 2.70; 95% CI, 1.41-5.16), and having 0 or 1 child (aOR, 3.46; 95% CI, 1.34-8.93). The CT score was based on these 3 criteria. The low-risk group was derived from values of the score (probability of CT, 1.3% [95% CI, 0-3.0]). Application of these criteria to the validation data set confirmed the diagnostic accuracy of the score (probability of CT, 0%). Sensitivity was 100% and specificity was 26.9% for the score in the validation data set. When applied to the validation data set, the score avoided 25.4% of CT tests and screened 100% of CT-infected women before surgical abortion. CONCLUSIONS: This easy-to-calculate score may prove useful for avoiding CT test in 25% of patients seeking surgical abortion.

Caesarean section at term: the relationship between neonatal respiratory morbidity and microviscosity in amniotic fluid.

OBJECTIVES: The incidence of neonatal respiratory morbidity following an elective caesarean section is 2-3 times higher than after a vaginal delivery. The microviscosity of surfactant phospholipids, as measured with fluorescence polarisation, is linked with the functional characteristics of fetal surfactant and thus fetal lung maturity, but so far this point has received little attention in newborns at term. The aim of the study is to evaluate the correlation between neonatal respiratory morbidity and amniotic microviscosity (Fluorescence Polarisation Index) in women undergoing caesarean section after 37 weeks' gestation. STUDY DESIGN: The files of 136 women who had undergone amniotic microviscosity studies during elective caesarean deliveries at term were anonymised. Amniotic fluid immaturity (AFI) was defined as a Fluorescence Polarisation Index higher than 0.335. RESULTS: Respiratory morbidity was observed in 10 babies (7.3%) and was independently associated with AFI (OR: 6.11 [95% CI, 1.20-31.1] with p=0.029) and maternal body mass index (OR: 1.12 [95% CI, 1.02-1.22] with p=0.019). Gestational age at the time of caesarean delivery was inversely associated with AFI (odds ratio, 0.46 [95% confidence interval, 0.29-0.71], p<0.001), especially before 39 weeks, and female gender was associated with an increased risk (odds ratio, 3.29 [95% confidence interval, 1.48-7.31], p=0.004). CONCLUSIONS: AFI assessed by amniotic microviscosity was significantly associated with respiratory morbidity and independently correlated with shorter gestational age especially before 39 weeks. This finding provides a physiological rationale for recommending delaying elective caesarean section delivery until 39 weeks of gestation to decrease the risk for respiratory morbidity.

Sexual and functional results after creation of a neovagina in women with Mayer-Rokitansky-Küster-Hauser syndrome: a comparison of nonsurgical and surgical procedures.

OBJECTIVE: To compare nonsurgical and surgical procedures for creation of a neovagina in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome in terms of sexual satisfaction. STUDY DESIGN: We report a cross-sectional study of 91 women with MRKH syndrome undergoing a neovagina creation procedure. They were members of the French National Association of Women with MRKH syndrome. We analyzed all answers to a questionnaire mailed to each woman. The questionnaire solicited short answers concerning the diagnosis and the neovagina procedure, and included the standardized FSFI (Female Sexual Function Index) questionnaire. All analyses were performed using the chi-squared test and Student's t-test. A p-value of <0.05 was considered statistically significant. RESULTS: Forty women answered the questionnaire. Twenty had been treated by Frank's method (non-surgical group) and 20 had undergone a surgical procedure, sigmoid vaginoplasty (12 cases) or Davidov's technique (8 cases) (surgical group). The mean time after neovagina creation was 7 years (range 1-44 years). The population characteristics did not differ significantly between the nonsurgical and surgical groups. The total FSFI score indicated good and similar functional results in the two groups (25.3±7.5 versus 25.3±8.0). CONCLUSIONS: Functional sexual outcomes after nonsurgical and surgical methods were similar. Therefore, the Frank's method should be proposed as first line therapy because it is less invasive than surgical procedures. In the case of failure of this technique or of refusal by the patient, surgical reconstruction may then be offered.

Pregnancy Rate after First Intra Cytoplasmic Sperm Injection- In Vitro Fertilisation Cycle in Patients with Endometrioma with or without Deep Infiltrating Endometriosis.

BACKGROUND: To evaluate the impact of the association of endometrioma with or without deep infiltrating endometriosis (DIE) after a first intra cytoplasmic sperm injection- in vitro fertilization (ICSI-IVF) cycle on pregnancy rate. MATERIALS AND METHODS: In this retrospective study, women with endometrioma who underwent a first ICSI-IVF cycle from January 2007 to June 2010 were reviewed for pregnancy rate. The main outcome measure was the clinical pregnancy rate. A multiple logistic regression (MLR) was performed; including all variables that were correlated to the conception rate. Only independent factors of pregnancy rate were included in a Recursive Partitioning (RP) model. RESULTS: The study population consisted of 104 patients (37 without DIE and 67 patients with associated DIE). Using multivariable analysis, a lower pregnancy rate was associated with the presence of DIE (OR=0.24 (95% CI: 0.085-0.7); p=0.009) and the use of ICSI (OR=0.23 (95% CI: 0.07-0.8); p=0.02). A higher pregnancy rate was associated with an anti-mullerian hormone (AMH) serum level over 1 ng/ml (OR=4.3 (95% CI: 1.1-19); p=0.049). A RP was built to predict pregnancy rate with good calibration [ROC AUC (95% CI) of 0.70 (0.65-0.75)]. CONCLUSION: Our data support that DIE associated with endometrioma in infertile patients has a negative impact on pregnancy rate after first ICSI-IVF cycle. Furthermore, our predictive model gives couples better information about the likelihood of conceiving.

Atypical hyperplasia of the breast: the black hole of routine breast cancer screening.

AIM: Determination of the prevalence, of the radiological and clinical characteristics, and outcome of atypical hyperplasia (AH) of the breast within a population subjected to routine screening (double-view mammography with double reading, performed every two years between 50 and 75 years of age). PATIENTS AND METHODS: The clinical and radiological records and histological findings of percutaneous and surgical biopsy specimens of sixty-eight patients presenting with AH were reviewed together with patient follow-up data after percutaneous and surgical biopsy. RESULTS: AH incidence in the population was 0.19‰ with the following distribution of lesions: atypical epithelial hyperplasia (AEH, 53%), columnar cell metaplasia with atypia (CCMA, 32%), and lobular intraepithelial neoplasia (LIN, 8%). The mean patient age was 58 years and 24% of patients were receiving hormone replacement therapy. The main radiological finding was the presence of microcalcifications for AEH and CCMA lesions in particular, and the mammograms were valid (correlation between American College of Radiology score and risk of lesion, only 3% of lesions were recognized on the second reading). A total of 13.7% of AH cases were underestimated and a real risk of AH progression was observed, regardless of whether or not surgical biopsy had been performed. CONCLUSION: The clinical and radiological characteristics of AH observed in a population subjected to routine breast cancer screening are identical to those for patients with the same lesions referred to specialist centers. Surgical biopsy remains the recommended option due to the risk of underestimation of lesions by percutaneous biopsy and the risk of progression justifies the need for continued close monitoring.

Screening for Chlamydia trachomatis using self-collected vaginal swabs at a public pregnancy termination clinic in France: results of a screen-and-treat policy.

OBJECTIVE: To assess the prevalence of Chlamydia trachomatis (CT) infection and the risk factors for CT infection among women presenting for abortion at a clinic in France. METHODS: Women seeking surgically induced abortions were systematically screened by PCR on self-collected vaginal swabs between January 1, 2010, and September 30, 2010. CT-positive women were treated with oral azithromycin (1 g) before the surgical procedure. RESULTS: Of the 978 women included in the study, 66 were CT positive. The prevalence was 6.7% (95% confidence intervals [CI] 5.1%-8.3%). The risk factors for CT infection were the following: age <30 years (Odds ratio [OR]: 2.0 [95% CI: 1.2-3.5]), a relationship status of single (OR: 2.2 [95% CI: 1.2-4.0]), having 0 or 1 child (OR: 5.2 [95% CI: 2.0-13.0]), not using contraception (OR: 2.4 [95% CI: 1.4-4.1]), and completing 11 weeks or more of gestation (OR: 2.1 [95% CI: 1.3-3.6]). Multiple logistic regression indicated that 4 factors--having 0 or 1 child, a single relationship status, no contraceptive use, and a gestation of 11 weeks or more--were independently associated with CT infection. The rate of postabortion infection among all patients was 0.4% (4/978). CONCLUSIONS: These results reveal a high prevalence (6.7%) of CT-positive patients among French women seeking induced abortions. Because it is not common practice to screen the general population for CT, screening before induced abortions seems relevant. A cost-effectiveness study is required to evaluate this screen-and-treat policy.

Cumulative pregnancy rate after ICSI-IVF in patients with colorectal endometriosis: results of a multicentre study.

BACKGROUND: There is currently no consensus about indications for surgery for infertility associated with colorectal endometriosis. The aim of this study was to evaluate cumulative pregnancy rates (CPRs) after ICSI-IVF cycles in patients with colorectal endometriosis and to identify determinant factors of fertility outcome. METHODS: Prospective longitudinal multicentre study from January 2005 to June 2011. We included 75 patients with colorectal endometriosis and proved infertility without prior surgery for deep infiltrating endometriosis. Univariable analysis was used to identify determinant factors of pregnancy rate. CPR was calculated using cumulative-incidence methods from log-rank test and Kaplan-Meier curves. For multivariable analysis, Cox proportional hazards model was used. RESULTS: For CPR per patient analysis, the total number of cycles was 113 and the median number of cycles per patient was 1 (range: 1-3). In the whole population the CPR per patient after three ICSI-IVF cycles was 68.6%. The CPR for patients with or without associated adenomyosis was 19 and 82.4%, respectively (P= 0.01). In addition, a patient age over 35 years (P= 0.02) and anti-Mullerian hormone serum level under 2 ng/ml (P= 0.02) were associated with a decreased CPR per patient. At multivariable analysis, adenomyosis [HR = 0.34, 95% CI (0.12-0.99), P= 0.49] was associated with a decreased CPR. CONCLUSIONS: Our data confirm that ICSI-IVF offers a high CPR per patient. However, determinant factors of CPR should be taken into account when informing couples of their options.

Involvement of ITIH5, a candidate gene for congenital uterovaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome), in female genital tract development.

The ITI (inter-trypsine inhibitor) gene family includes five genes (ITIH1 to ITIH5) that encode proteins involved in the dynamics of the extracellular matrix (ECM). ITIH5 was found inactivated by partial deletion in a case of congenital uterovaginal aplasia, a human rare disease also called Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. The aim of the present study was to analyze the expression of ITIH5 in the uterus in adult life and during embryogenesis in order to establish the involvement of this gene in both normal and pathological conditions of uterus development. This was achieved in mice by reverse transcription-quantitative PCR, whole-mount hybridization, and Western blot analysis. Itih5 expression was much stronger in female genital tract primordia (Müllerian ducts) and derivatives than elsewhere in the body. This gene was strongly expressed during pregnancy and development of the female genital tract, indicating that the encoded protein probably had an important function in the uterus during these periods. Two different specific isoforms of the protein were detected in Müllerian derivatives during embryogenesis and in adults. Although ITIH genes are expected to be predominantly expressed in the liver, ITIH5 is mainly expressed in the uterus during development and adult life. This tends to indicate an additional and specific role of this gene in the female reproductive tract, and furthermore reinforces ITIH5 as a putative candidate gene for MRKH syndrome.

Isolated skin recurrence following salvage mastectomy for intramammary recurrence (after initial breast conservation therapy): is it a fatal event?

AIMS: The authors analyzed the outcome of patients with Isolated Skin Recurrence After Salvage Mastectomy (ISRASM) performed after conservative treatment for breast carcinoma, taking into account initial tumor characteristics, intramammary recurrence (first recurrence) characteristics, local skin recurrence (second recurrence) characteristics, and the type of treatment at each stage of the breast cancer continuum. METHODS: Forty-two patients who had ISRASM between 1976 and 2007 were included in this retrospective study. Twenty-six factors were studied in univariate and multivariate analyses. RESULTS: Mean Overall Survival (OS) was 70.3 (±4.1) months. The 5-year OS rate was 66.6%. 31% of patients did not present any recurrence, 52% had locoregional recurrence and 14% metastatic recurrence following ISRASM. Univariate analysis showed that 4 prognostic factors were significantly related to OS and/or Disease-Free Survival (DFS): (1) initial chemotherapy after primary breast cancer (P = 0.09 and 0.01 respectively), (2) presence of emboli at the site of intramammary recurrence (first recurrence) (P = 0.02 and 0.03), (3) interval between first and second surgery of less than 3 years (P = 0.09 and 0.0003), and (4) inflammatory skin involvement at ISRASM (P = 0.005 and 0.17). Multivariate analysis showed that presence of emboli at the site of intramammary recurrence was significantly related to OS and that an interval between first and second recurrence of less than 3 years was significantly related to DFS. CONCLUSION: Our results show that ISRASM affects a group of breast cancer patients with predominantly local rather than metastatic disease. Prognostic factors depend on characteristics at initial breast cancer, first recurrence and second recurrence. Evidence-based guidelines are still required for ISRASM management.

Utero-vaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome) associated with deletions in known DiGeorge or DiGeorge-like loci.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. The uterovaginal aplasia is either isolated (type I) or more frequently associated with other malformations (type II or Müllerian Renal Cervico-thoracic Somite (MURCS) association), some of which belong to the malformation spectrum of DiGeorge phenotype (DGS). Its etiology remains poorly understood. Thus the phenotypic manifestations of MRKH and DGS overlap suggesting a possible genetic link. This would potentially have clinical consequences. METHODS: We searched DiGeorge critical chromosomal regions for chromosomal anomalies in a cohort of 57 subjects with uterovaginal aplasia (55 women and 2 aborted fetuses). For this candidate locus approach, we used a multiplex ligation-dependent probe amplification (MLPA) assay based on a kit designed for investigation of the chromosomal regions known to be involved in DGS.The deletions detected were validated by Duplex PCR/liquid chromatography (DP/LC) and/or array-CGH analysis. RESULTS: We found deletions in four probands within the four chromosomal loci 4q34-qter, 8p23.1, 10p14 and 22q11.2 implicated in almost all cases of DGS syndrome. CONCLUSION: Uterovaginal aplasia appears to be an additional feature of the broad spectrum of the DGS phenotype. The DiGeorge critical chromosomal regions may be candidate loci for a subset of MRKH syndrome (MURCS association) individuals. However, the genes mapping at the sites of these deletions involved in uterovaginal anomalies remain to be determined. These findings have consequences for clinical investigations, the care of patients and their relatives, and genetic counseling.

Perinatal morbidity and mortality in twin pregnancies with dichorionic placentas following assisted reproductive techniques or ovarian induction alone: a comparative study.

OBJECTIVE: To compare maternal and perinatal outcome in non-spontaneously and spontaneously conceived dichorionic twin pregnancies. STUDY DESIGN: We report a retrospective study of all 350 twin pregnancies delivered ≥22 weeks of gestation between January 1, 2001 and December 31, 2005 in a tertiary maternity unit. We compared maternal outcome, perinatal morbidity and neonatal mortality between spontaneous and non-spontaneous dichorionic twin pregnancies, with a subgroup analysis separating pregnancies following assisted reproduction technology (ART group) from those following ovarian induction alone (OI group). Generalized linear model and multivariate analysis were performed. RESULTS: The proportion of primiparous women and the mean maternal age were higher in the non-spontaneously conceived dichorionic twin pregnancy group as expected (70.2% vs. 38.2%, p<0.001 and 32.1 ± 3.8 vs. 30.7 ± 4.6 years, p<0.01). Multivariate analysis, adjusted for maternal age and parity, revealed that non-spontaneously conceived dichorionic twin pregnancies were associated with a higher risk of very preterm birth (OR 2.20, 95% confidence interval 1.02-4.77, p<0.05), low birth weight (1.77, 1.21-2.61, p<0.01), very low birth weight (1.99, 1.13-3.49, p<0.05), NICU admission (1.66, 1.14-2.43, p<0.01), and fetal or neonatal death (3.21, 1.30-7.95, p<0.05). Multivariate analysis confirmed that the mean gestational age (p<0.01) and mean birth weight of the first (p<0.05) and second twins (p<0.01) were lower in the non-spontaneously conceived dichorionic twin pregnancy group. These associations were confirmed in the OI group analysis (n=39) but not in the ART group (n=65). Ovarian induction was associated with an increase in the risk of preterm and very preterm births (2.25, 1.06-4.75, p<0.05 and 3.47, 1.42-8.49, p<0.01, respectively), low and very low birth weights (2.87, 1.63-5.05, p<0.001 and 2.59, 1.33-5.07, p<0.01, respectively), NICU admission (2.92, 1.67-5.11, p<0.001) and fetal or neonatal death (4.20, 1.40-12.56, p<0.05). The mean gestational age (p<0.001) and mean birth weight of the first (p<0.01) and second twins (p<0.001) were also lower in the OI group. CONCLUSIONS: Twin pregnancies with dichorionic placentation following non-spontaneously conceived pregnancy are associated with a higher risk of adverse perinatal outcome compared with dichorionic spontaneously conceived twin pregnancies especially in case of ovarian induction alone.