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.

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.

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.

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.

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.

Radioisotopic location of the sentinel node in vaginal mucous melanoma before laparoscopic sampling.

A 66-year-old woman was diagnosed with vaginal melanoma. Sentinel node mapping was performed using Tc sulfur colloid. Planar scintigraphic acquisitions detected 2 sentinel nodes in the right external iliac region, which were laparoscopically removed with an anterior vaginectomy. Sentinel node mapping is feasible in cases of vaginal melanoma.

Restoration of ovulation after unilateral ovariectomy in a woman with McCune-Albright syndrome: a case report.

INTRODUCTION: McCune-Albright syndrome (MAS) is characterized by peripheral precocious puberty, café-au-lait spots, and polyostotic fibrous dysplasia. This syndrome is due to a post-zygotic mutation of the GNAS1 gene with mosaic distribution and unilateral predominance. Clinical manifestations depend on the tissues carrying the mutation. We describe the ovarian function before and after unilateral ovariectomy in a woman with MAS and bilateral distribution of the GNAS1 gene mutation. CASE REPORT: A 33-year-old patient, previously diagnosed as having MAS, presented irregular menstrual cycles (30-180 days) and monophasic temperature curves. Transvaginal ultrasound and blood tests were repeated at 3-day intervals over 3 months. Findings included a persistent quiescent left ovary, a persistent polycystic right ovary, constantly high estradiol-17beta (E2) levels, and very low FSH and LH levels. She also presented severe persistent pelvic pain. Because of unilateral ovarian activity, a unilateral right ovariectomy was performed as well as biopsy of the remaining left ovary. A GNAS1 gene mutation was identified in both ovaries. A regular monthly menstrual cycle was immediately restored. On day 3 of the menstrual cycle, E2 level was 30 pg/ml, FSH level was 7.5 mIU/ml, and LH level was 6.4 mIU/ml. On day 17, pelvic ultrasound showed one follicle of 25 mm in the left ovary. On day 21, the progesterone level was 13.1 ng/ml. DISCUSSION: This is the first report of ovulation being restored following unilateral ovariectomy in an adult patient suffering from severe MAS with GNAS1 gene mutation identified in both ovaries.

Phenotypic variability of a 4q34-->qter inherited deletion: MRKH syndrome in the daughter, cardiac defect and Fallopian tube cancer in the mother.

Terminal deletions of the long arm of chromosome 4 are associated with a recognizable phenotype consisting of dysmorphic facial features, cleft palate, upper and lower limb malformations, cardiac defects and growth and mental retardation. Here we report on two female patients, a mother and her daughter, carrying the same 4q34-->qter deletion but presenting with a different phenotype. The mother's presentation is consistent with previous findings in patients with terminal deletions of the long arm of chromosome 4. However, she presented at the age of 54years with bilateral serous carcinoma of the Fallopian tubes, a rare gynaecologic cancer that might be attributed to the haploinsufficiency of the tumor suppressor gene FAT. The daughter presented isolated congenital aplasia of the uterus and vagina, the prime feature of the MRKH syndrome. This has not been described before in association with a 46,XX,del(4)(q34qter).