Bacterial infection in endometriosis: a silver-lining for the development of new non-hormonal therapy?

The pathogenesis of endometriosis is a hotly debated topic, yet still cloaked in multiple layers of hypothetical theories. A recent report raises the possibility that bacterial infection, especially those of the genus Fusobacterium, may be the cause of endometriosis, at least in certain women. More importantly, the demonstration that treatment with broad-spectrum antibiotics significantly reduced the size of lesions in a mouse endometriosis model rekindles the hope for new non-hormonal treatments. The development of new therapies has been plagued by strings of unsuccessful clinical trials over the last two decades. Is this antibiotic therapy, a silver lining for the research and development of non-hormonal drugs for endometriosis?

Clinical Management of Infertility Associated with Endometriosis.

OBJECTIVE: This study aimed to review recent data that affected the clinical management of infertility associated with endometriosis. DATA SOURCES: We completed a PubMed review of all articles that included the following keywords: endometriosis, infertility, IVF, and ART. STUDY SELECTION: A study was selected based on the pertinence of the topic addressed in relation to the study's set objectives. DATA EXTRACTION AND SYNTHESIS: All identified articles were first assessed based on a review of the abstract. Pertinent articles were reviewed in depth. CONCLUSION: Endometriosis interferes with natural conception primarily by altering the quality of gametes-oocytes and sperm-and early-stage embryos. On the contrary, recent data indicate that gametes and early-stage embryos are not altered in the case of ART. Surgery-a classical approach in yesteryears-does appear to improve ART outcomes and may affect ovarian reserve and the number of oocytes retrieved in ART. Surgery is thus more rarely opted for today and only when necessary; proceeding to fertility preservation prior to surgery is recommended. When ART is performed in women with endometriosis, it is recommended to use an antagonist or progesterone-primed ovarian stimulation approach followed by deferred embryo transfer. In this case, GnRH (gonadotropin releasing hormone) agonist is preferred for triggering ovulation, as it limits the risk of cyst formation as well as ovarian hyperstimulation syndrome. Frozen embryo transfers are best performed in E2 (estradiol) and progesterone replacement cycle.

Successful ART outcome in a woman with McCune-Albright syndrome: a case report and literature review.

McCune-Albright syndrome (MAS) is a rare genetic disease affecting multiple organs, including endocrine tissues. This endocrinopathy is sometimes responsible for infertility, as it may induce an independent functioning of the ovaries leading to anovulatory cycles. This case report describes the infertility journey of a 22-year-old female who had early puberty and irregular periods with high estrogen and progesterone levels, low FSH and LH (on day 3 of her menstrual cycle), and a multi-cystic right ovary. She received several infertility treatments: initially in vitro oocyte maturation (IVM) followed by cyst transvaginal ultrasound-guided aspiration, all unsuccessful. A right hemi-ovariectomy was performed that eventually restored regular cycles and made it possible to perform ovarian stimulation (OS) and in vitro fertilization (IVF). Live birth was obtained after the first embryo transfer.

Limits imposed by the experimental design of a large prospective non-inferiority study on PGT-A invalidate many of the conclusions.

The New England Journal of Medicine recently published a large study addressing the efficacy of preimplantation genetic testing for aneuploidy (PGT-A). The 14-centre randomized control non-inferiority trial used cumulative live birth rate (CLBR) as a clinical endpoint to examine the value of PGT-A and concluded that conventional IVF was not inferior to IVF with PGT-A. Unfortunately, the experimental design was highly flawed; and in fact, the data generated in the study do not support the major conclusions presented in the publication. The embryos in each patient's three-embryo pool, which were available for transfer, were selected solely by morphology. The investigators then randomized patients to either the PGT-A group or the control group. It is important to note that PGT-A screening in the study group was done only after the embryos were selected. PGT-A was not really used in a meaningful way, which would have been for the PGT-A results to help in selecting which embryos would be in the three-embryo group. Thus, the outcomes were wholly determined prior to the study intervention. The ultimate delivery rate for each group of three embryos was determined when they were selected by morphology. The randomization, which occurred after embryo selection, would assure equal distribution of those cohorts destined to deliver and those destined to fail to the two study groups, the PGT-A and control groups. Thus, there was no potential for PGT-A to enhance selection and thus no possible way to improve the cumulative outcomes. Since there was no possible way for the control group to be inferior, the experimental design precluded any chance of evaluating the primary endpoint of the study. The primary question of the study was never evaluated. Another serious flaw was that the study was initiated prior to knowing how to interpret the data provided in the PGT-A analytical result. Specifically, the design excluded mosaic embryos from transfer despite the literature demonstrating the significant reproductive potential for these embryos. When accounting for the lost deliveries induced by this non-evidence-based decision, the expected delivery rates in the two groups become virtually identical. That is an important issue because the data from the study actually demonstrate the safety of PGT-A without diminution in outcomes from the impact of trophectoderm biopsy or the discarding of competent embryos which had wrongfully been considered aneuploid. A final serious flaw in the experimental design and interpretation of the data surrounding the issue of the miscarriage rate. The investigators noted that the miscarriage rate was lower in the PGT-A group but stated that its impact was insufficient to alter the CLBR. Of course, by design, the CLBRs were limited to being equivalent. There was no potential for enhanced outcomes in the PGT-A group and thus no possibility that the lower risk of miscarriage in the PGT-A group would raise the CLBR. The benefit of a lower miscarriage rate is real and significant. Its relevance should not be diminished based on the lack of a change in the CLBR since that was never possible in this study. The investigators of the study concluded that the CLBR with conventional ART is equivalent to that with PGT-A, but a simple review of the experiment reassigns their genuine findings to those of a safety study. Significantly, the data in the study demonstrate that the intervention of PGT-A is safe. This study neither supports nor refutes the efficacy of clinical PGT-A.

Evolving clinical challenges in uterus transplantation.

Before the first live birth following uterus transplantation (UTx) in 2014, the 1-2% of women with an absent or non-functional uterus had no hope of childbearing. With 64 cases of UTx and 34 births reported in the scientific literature, this emerging technology has the potential for translation into mainstream clinical practice. However, limitations currently include donor availability, recipient suitability, surgical challenges regarding success and complications, and recipient management after UTx and during pregnancy. This review considers these challenges and ways to overcome them so that UTx could become part of the reproductive specialist's armamentarium when counselling patients with uterine factor infertility.

Previous caesarean delivery and the presence of caesarean scar defects could affect pregnancy outcomes after in vitro fertilization frozen-thawed embryo transfer: a retrospective cohort study.

BACKGROUND: Due to various iatrogenic and social factors, the global caesarean delivery (CD) rate has risen sharply in the past 30 years. It is more complicated and dangerous for women with a scarred uterus to experience pregnancy again than for women with a previous vaginal delivery (VD). In this study we investigated the impact of previous caesarean delivery (CD) and caesarean scar defects (CSDs) on pregnancy outcomes after in vitro fertilization frozen-thawed embryo transfer (IVF-FET). METHODS: We conducted a retrospective cohort study that included 1122 women aged < 40 years who had a history of only one parturition (after 28 weeks of pregnancy) and who underwent their first FET cycle between January 2014 and January 2020. Patients were divided into the CD group, VD group, and CSD group. Thereafter, according to the number of transferred embryos, the CD, VD, and CSD groups were divided into the single embryo transfer (SET) group and the double embryo transfer (DET) group. Outcome measures in this study were live birth, clinical pregnancy, multiple pregnancy, ectopic pregnancy, pregnancy loss, pregnancy complications, preterm birth, and neonatal birth weight. Multivariate logistic regression was performed to evaluate the relationship between pregnancy outcomes and CD. RESULTS: In SET patients, the clinical pregnancy and live birth rates were decreased in the CSD group compared with the VD and CD groups. In DET patients, the clinical pregnancy and live birth rates were significantly lower in theCSD group than in the CD and VD groups. After adjustment for confounders, previous CD and CSD were associated with a significantly lower clinical pregnancy rate and live birth rate than previous VD in the total sample. This effect was observed in DET patients, but not in SET patients. Additionally, DET patients with previous CD had a significantly higher multiple pregnancy rate (AOR = 0.47, 95% CI = 0.29, 0.75, P = 0.002) than those with previous VD, but no significant associations were observed in CSD and multiple pregnancies (AOR = 0.55, 95% CI = 0.23, 1.34, P = 0.192) between DET patients with CD and those with VD after adjusting for potential confounders. CONCLUSIONS: Our study showed that during an FET cycle, previous CD and the presence of a CSD could negatively affect pregnancy outcomes especially in DET patients.

MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining.

PURPOSE: The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138. METHODS: This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC. RESULTS: Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761-0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138. CONCLUSION: IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.

Recurrent implantation failure: how common is it?

PURPOSE OF REVIEW: To clarify a lingering issue, the true incidence of repeated implantation failures (RIF) in women undergoing successive frozen euploid single embryo transfers (FE-SET). RECENT FINDINGS: As not all Assisted reproductive techinique (ART) attempts are crowned by success, it has been questioned since incept of ART whether failures resulted from an embryonic or endometrial cause. RIF has received no precise definition but a trend has existed toward setting a more stringent definition, as reproductive biology has become more effective and ART success rates improved. No scientific society has yet convened on a universally accepted definition. The advent of effective and well tolerated pregestational testing of embryos for aneuploidy (PGT-A) has allowed to not transfer aneuploid embryos, which are bound not to succeed. This, therefore, justify revisiting the concept of RIF when only euploid embryos are transferred. SUMMARY: Contrary to lingering beliefs, the results of our study indicate that RIF following three successive euploid embryo transfers in a morphologically normal endometrium is a rare occurrence (<5%). This supports the concept that ART failures mainly result from embryonic causes. Our data also propose a new - functional - definition of RIF being an ART failure following 3 successive FE-SET attempts. Our findings, therefore seriously question the soundness of prescribing the often complex and expensive endometrial testing procedures that largely publicized for treating RIF.

Managing an obstetrics and gynaecology department in time of COVID pandemic: safety and efficacy first at Foch hospital.

Obstetrics and Gynecology department in France were not ready for the outbreak of the COVID pandemic, but ingenuity and dedication of personnel allowed to perform safely and avoid nocomial transmission of COVID.

Chronic Endometritis, a Common Disease Hidden Behind Endometrial Polyps in Premenopausal Women: First Evidence From a Case-Control Study.

STUDY OBJECTIVE: To investigate the correlation between endometrial polyps (EPs) and chronic endometritis (CE). DESIGN: Single-center retrospective case-control study. SETTING: Academic center. PATIENTS: A total of 480 premenopausal women with abnormal uterine bleeding (AUB) were enrolled. Group A included 240 women suffering from EPs (diagnosed by hysteroscopy and histology), and group B included 240 patients without EPs at hysteroscopy. INTERVENTIONS: In group A, 2 separate samples were obtained from the EPs (group A polyps) and endometrium (group A endometrium). In group B, a single sample of endometrial tissue was evaluated (group B endometrium). All tissue samples were subjected to immunohistochemistry for CD-138 for plasma cell identification. MEASUREMENTS AND MAIN RESULTS: The primary study endpoint was to compare the rates of CE in group A endometrium versus group B endometrium. The secondary endpoint was to evaluate the consistency in CD-138 immunoreactivity between group A polyps and compared with group A endometrium. A higher prevalence of CE was observed in group A endometrium compared with group B endometrium (p < .0001). The total percentage of EPs showing CD-138 positivity was 76.7% (184 of 240). CE was more frequent in women with CD-138+ EPs compared to those with CD-138- EPs (p < .0001). CONCLUSIONS: EPs were commonly associated with CE in the premenopausal women suffering from AUB. Moreover, the majority of EPs were positive for CD-138 staining, suggesting a possible hidden association between chronic inflammation and EPs.

Live birth rate following frozen-thawed blastocyst transfer is higher with blastocysts expanded on Day 5 than on Day 6.

STUDY QUESTION: The aim of this study was to evaluate the live birth rate (LBR) after frozen-thawed Day 5 (D5) and Day 6 (D6) blastocyst transfers. SUMMARY ANSWER: LBR following frozen-thawed blastocyst transfer is significantly lower with D6 than with D5 blastocyst regardless of embryo quality. WHAT IS KNOWN ALREADY: During fresh embryo transfer cycles, pregnancy rates (PR) are significantly higher when transferring blastocysts expanded on D5 compared with slow developing blastocysts (D6). In programmed thawed blastocyst transfer (TBT) cycles, the same clinical outcomes should be expected when transferring D5 or D6 blastocysts because of endometrial/embryonic synchronization due to hormonal priming of endometrial receptivity. However, the impact of delayed blastocyst expansion at D6 on clinical outcomes remains unclear. Some reports have shown higher PRs after D5 TBT compared with those of D6, while others have shown equivalent TBT outcomes after D5 and D6 cryopreserved blastocysts transfers. STUDY, DESIGN, SIZE, DURATION: This retrospective cohort follow-up study included 1347 single autologous frozen-thawed blastocyst transfers performed between January 2012 and December 2015 at a tertiary care university hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: All of the patients scheduled for TBT were allocated to two groups according to the day of blastocyst expansion: on D5 (n = 994) or on D6 (n = 353). The primary outcome was LBR per embryo transfer in the first blastocyst thawing cycle. Secondary outcomes were clinical pregnancy rate (cPR), early miscarriage rate and neonatal outcomes following TBT for the two groups. Statistical analyses were conducted using univariate and multivariate logistic regression model. MAIN RESULTS AND THE ROLE OF CHANCE: The LBR was significantly increased in the D5 group compared to the D6 group [294/994 (29.6%) versus 60/353 (17.0%); P < 0.001]. The cPR was also higher when blastocysts were vitrified on D5 compared with those vitrified on D6 [429/994 (43.2%) versus 95/353 (26.9%); P < 0.001]. No significant differences were found between groups in terms of early miscarriage rate (P = 0.862). More good-quality embryos (defined as an B3-B4 or B5 embryo ≥BB according to the grading scale proposed by Gardner) were transferred in the D5 group than in the D6 group [807 (81.2%) versus 214 (60.6%); P < 0.001]. However, a comparison of TBT cycles with equal embryo quality (good versus low) also supported the superiority of D5 blastocysts. Concerning neonatal outcomes, the D5 group infants had a lower mean birth weight compared to those of the D6 group (P = 0.001). In addition, a significantly shorter gestational age at birth is reported in the D5 blastocyst group as compared to the D6 group (P = 0.004). After multivariate logistic regression taking into account potential confounders such as the women's age, number of previous IVF/ICSI procedures, the day of the blastocyst vitrification (D5 or D6) and embryo quality, blastocyst expansion at D6 was independently associated with a significant decrease in LBR compared to D5 expanded-blastocysts (OR 0.52; 95% CI 0.38-0.72; P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The poor predictive value of the morphological approach in embryo selection could constitute a limitation in this study. However, blastocyst quality was evaluated similarly in both groups. WIDER IMPLICATIONS OF THE FINDINGS: The LBR following frozen-thawed blastocyst transfer was significantly lower with D6 than with D5 blastocysts, regardless of their quality. These results could affect cryopreservation procedures as they suggest that the use of D5-expanded blastocysts for TBT may be preferred in order to shorten the time of conceiving. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology.

BACKGROUND: Chronic endometritis is a persistent inflammation of the endometrial mucosa caused by bacterial pathogens such as Enterobacteriaceae, Enterococcus, Streptococcus, Staphylococcus, Mycoplasma, and Ureaplasma. Although chronic endometritis can be asymptomatic, it is found in up to 40% of infertile patients and is responsible for repeated implantation failure and recurrent miscarriage. Diagnosis of chronic endometritis is based on hysteroscopy of the uterine cavity, endometrial biopsy with plasma cells being identified histologically, while specific treatment is determined based on microbial culture. However, not all microorganisms implicated are easily or readily culturable needing a turnaround time of up to 1 week. OBJECTIVE: We sought to develop a molecular diagnostic tool for chronic endometritis based on real-time polymerase chain reaction equivalent to using the 3 classic methods together, overcoming the bias of using any of them alone. STUDY DESIGN: Endometrial samples from patients assessed for chronic endometritis (n = 113) using at least 1 or several conventional diagnostic methods namely histology, hysteroscopy, and/or microbial culture, were blindly evaluated by real-time polymerase chain reaction for the presence of 9 chronic endometritis pathogens: Chlamydia trachomatis, Enterococcus, Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Mycoplasma hominis, Neisseria gonorrhoeae, Staphylococcus, and Streptococcus. The sensitivity and specificity of the molecular analysis vs the classic diagnostic techniques were compared in the 65 patients assessed by all 3 recognized classic methods. RESULTS: The molecular method showed concordant results with histological diagnosis in 30 samples (14 double positive and 16 double negative) with a matching accuracy of 46.15%. Concordance of molecular and hysteroscopic diagnosis was observed in 38 samples (37 double positive and 1 double negative), with an accuracy of 58.46%. When the molecular method was compared to microbial culture, concordance was present in 37 samples (22 double positive and 15 double negative), a matching rate of 56.92%. When cases of potential contamination and/or noncultivable bacteria were considered, the accuracy increased to 66.15%. Of these 65 patients, only 27 patients had consistent histological + hysteroscopic diagnosis, revealing 58.64% of nonconcordant results. Only 13 of 65 patients (20%) had consistent histology + hysteroscopy + microbial culture results. In these cases, the molecular microbiology matched in 10 cases showing a diagnostic accuracy of 76.92%. Interestingly, the molecular microbiology confirmed over half of the isolated pathogens and provided additional detection of nonculturable microorganisms. These results were confirmed by the microbiome assessed by next-generation sequencing. In the endometrial samples with concordant histology + hysteroscopy + microbial culture results, the molecular microbiology diagnosis demonstrates 75% sensitivity, 100% specificity, 100% positive and 25% negative predictive values, and 0% false-positive and 25% false-negative rates. CONCLUSION: The molecular microbiology method describe herein is a fast and inexpensive diagnostic tool that allows for the identification of culturable and nonculturable endometrial pathogens associated with chronic endometritis. The results obtained were similar to all 3 classic diagnostic methods together with a degree of concordance of 76.92% providing an opportunity to improve the clinical management of infertile patients with a risk of experiencing this ghost endometrial pathology.

Extended culture of poor-quality supernumerary embryos improves ART outcomes.

PURPOSE: The aims of this study were to investigate the possible benefits of extending the culture of poor-quality day-2 embryos (PQE) versus good-quality embryos (GQE) and to identify factors associated with pregnancy and live birth when transferring frozen-thawed blastocysts originating from GQE and PQE. METHODS: This is a retrospective cohort follow-up study performed between November 2012 and February 2015 at the IVF Laboratory Unit of Cochin University Hospital (Paris, France) including 3108 day-2 supernumerary embryos resulting from 1237 IVF/ICSI cycles. RESULTS: Total blastulation rate was 67.2% from GQE and 48.7% from PQE. Percentage of good-quality blastocysts was 60.7 and 47.9% respectively including 14.7 and 7.3% top-quality blastocysts. A total of 150 blastocysts originating from GQE and 729 from PQE were frozen, and then, 37 and 164 were thawed and transferred respectively resulting in 19 (51.4%) and 61 (37.9%) clinical pregnancies with 13 (35.1%) deliveries from GQE and 32 (19.9%) from PQE (p = 0.046) without any difference in neonatal outcomes. Quality of blastocysts that resulted in live birth was similar in the two groups. Women < 35 years old and day-5 blastocyst expansion were predictive of pregnancy and live birth. CONCLUSIONS: (i) PQE are able to reach the blastocyst stage, to implant, and to give healthy babies and (ii) women age and day of blastocyst expansion are predictive of pregnancy and live birth.

A randomized controlled trial comparing the efficacy and safety of two HMG preparations gaining their LH bioactivity from different HCG sources.

In this prospective, controlled, randomized, multicentre, non-inferiority study, efficacy and safety of two HMG preparations (Menopur®- Ferring and Meriofert®- IBSA Institut Biochimique SA) for ovarian stimulation were compared (270 women undergoing IVF aged between 18 and 39 years; BMI 30 kg/m2 or less; less than three prior completed assisted reproduction technique cycles). A standard long down-regulation with gonadotrophin-releasing hormone agonist protocol, with HCG triggering was used; primary end-point was total number of oocytes retrieved; attention was paid toovarian hyperstimulation syndrome (OHSS). No statistically significant differences between the treatment groups were reported for most of the clinically significant end-points, including embryo quality, fertilization rate, implantation rate, ongoing pregnancy rate and live birth rate. Total number of oocytes retrieved was higher in the new HMG group compared with the reference (11.6 ± 6.6 and 9.7 ± 5.9, respectively, with a 95% CI of the difference equal +0.43 to +3.43). Increased number of oocytes was obtained through a shorter stimulation, but HMG units per oocyte retrieved were equivalent. The safety profile of the products for frequency of ovarian hyperstimulation syndrome was the same. This study showed that the new HMG preparation is a viable alternative for conducting ovarian stimulation in IVF cycles.

Prognostic factors for assisted reproductive technology in women with endometriosis-related infertility.

BACKGROUND: Assisted reproductive technology is one of the therapeutic options offered for managing endometriosis-associated infertility. Yet, published data on assisted reproductive technology outcome in women affected by endometriosis are conflicting and the determinant factors for pregnancy chances unclear. OBJECTIVE: We sought to evaluate assisted reproductive technology outcomes in a series of 359 endometriosis patients, to identify prognostic factors and determine if there is an impact of the endometriosis phenotype. STUDY DESIGN: This was a retrospective observational cohort study, including 359 consecutive endometriosis patients undergoing in vitro fertilization or intracytoplasmic sperm injection, from June 2005 through February 2013 at a university hospital. Endometriotic lesions were classified into 3 phenotypes-superficial peritoneal endometriosis, endometrioma, or deep infiltrating endometriosis-based on imaging criteria (transvaginal ultrasound, magnetic resonance imaging); histological proof confirmed the diagnosis in women with a history of surgery for endometriosis. Main outcome measures were clinical pregnancy rates and live birth rates per cycle and per embryo transfer. Prognostic factors of assisted reproductive technology outcome were identified by comparing women who became pregnant and those who did not, using univariate and adjusted multiple logistic regression models. RESULTS: In all, 359 endometriosis patients underwent 720 assisted reproductive technology cycles. In all, 158 (44%) patients became pregnant, and 114 (31.8%) had a live birth. The clinical pregnancy rate and the live birth rate per embryo transfer were 36.4% and 22.8%, respectively. The endometriosis phenotype (superficial endometriosis, endometrioma, or deep infiltrating endometriosis) had no impact on assisted reproductive technology outcomes. After multivariate analysis, history of surgery for endometriosis (odds ratio, 0.14; 95% confidence ratio, 0.06-0.38) or past surgery for endometrioma (odds ratio, 0.39; 95% confidence ratio, 0.18-0.84) were independent factors associated with lower pregnancy rates. Anti-müllerian hormone levels <2 ng/mL (odds ratio, 0.51; 95% confidence ratio, 0.28-0.91) and antral follicle count <10 (odds ratio, 0.27; 95% confidence ratio, 0.14-0.53) were also associated with negative assisted reproductive technology outcomes. CONCLUSION: The endometriosis phenotype seems to have no impact on assisted reproductive technology results. An altered ovarian reserve and a previous surgery for endometriosis and/or endometrioma are associated with decreased pregnancy rates.

Luteal-phase support in assisted reproduction treatment: real-life practices reported worldwide by an updated website-based survey.

An updated worldwide web-based survey assessed the real-life clinical practices regarding luteal-phase supplementation (LPS) in assisted reproduction. This survey looked for changes since a former survey conducted nearly 3years earlier. The survey questions were: If you support the luteal phase, when do you start the regimen you are using?; Which agent/route is your treatment of choice to support the luteal phase?; If you use vaginal progesterone, which formulation do you use?; and How long you continue progesterone supplementation if the patient conceived? Data were obtained from 408 centres (82 countries) representing 284,600 IVF cycles/year. The findings were: (i) most practitioners (80% of cycles) start LPS on the day of egg collection; (ii) in >90%, a vaginal progesterone product is used (77% as a single agent and 17% in combination with i.m. progesterone), while human chorionic gonadotrophin as a single agent for LPS is not being used at all; and (iii) in 72% of cycles, LPS is administered until 8-10weeks' gestation or beyond. When compared with the initial survey, the results of this survey are encouraging as there is a clear shift towards a more unified and evidence-based approach to LPS in IVF cycles. This updated worldwide web-based survey assessed the actual real-life clinical practices regarding luteal-phase supplementation (LPS) in assisted reproduction. Specifically, this survey looked for changes since an initial survey conducted nearly 3years earlier. The survey included the following questions: If you support the luteal phase, when do you start the regimen you are using?; Which agent/route is your treatment of choice to support the luteal phase?; If you use vaginal progesterone, which formulation do you use?; and How long you continue progesterone supplementation if the patient conceived? Data from 408 centres in 82 countries representing a total of 284,600 IVF cycles/year were included. Most practitioners (80% of cycles) start LPS on the day of egg collection and in more than 90% a vaginal progesterone product is used for LPS (in 77% as a single agent and in 17% in combination with i.m. progesterone). As a single agent for LPS, human chorionic gonadotrophin is not being used at all. Regarding the duration of supplementation, in 72% of cycles, LPS is administered until 8-10weeks' gestation or beyond. When compared with the initial survey from 2009, the results of this updated survey are encouraging as there is a clear shift towards a more unified and evidence-based approach to luteal-phase support in IVF cycles. Nevertheless, although there is no firm evidence supporting the continuation of LPS after the demonstration of fetal heart beat on ultrasound, this remains the common practice of the majority of assisted reproduction centres worldwide.

Dual ovarian stimulation is a new viable option for enhancing the oocyte yield when the time for assisted reproductive technnology is limited.

Ovarian stimulation improves assisted reproductive technology outcome by increasing the number of oocytes available for insemination and in-vitro handling. A recent Duplex protocol features a dual stimulation, with the second stimulation started immediately after the first oocyte retrieval. Remarkably, the Duplex protocol is unexpectadly well tolerated by women and provides twice as many oocytes and embryos as a regular antagonist protocol in less than 30 days.

AMH concentration is not related to effective time to pregnancy in women who conceive naturally.

This study determined whether anti-Müllerian hormone (AMH) concentration influences the time necessary to conceive a live-born child--effective time to pregnancy (eTTP)--in a population of women who conceived naturally. This is an observational study of 87 women with a planned spontaneous pregnancy resulting in a live birth. eTTP was assessed retrospectively by a questionnaire and AMH was measured in a frozen serum sample from first trimester of pregnancy. eTTP was correlated with age (r=-0.24, P=0.02), but not with AMH (r=-0.10) or body mass index (r=0.05). With logistic regressions, the only variable that affected the probability of pregnancy within 3 or 6 months was age, irrespective of whether an AMH concentration limit of 1.0 ng/ml or 2.0 ng/ml was chosen. In conclusion, this study suggests that there is no relationship between AMH concentration and eTTP and therefore speaks against determining AMH in women who are not infertile for the purpose of predicting their chances of pregnancy. The findings are concordant with previous reports describing AMH as a quantitative but not a qualitative marker of ovarian reserve and therefore does not reflect a woman's ability to become pregnant. Anti-Müllerian hormone (AMH) is secreted by small growing ovarian follicles and reflects a woman's ovarian reserve - the number of primordial follicles at a given time. AMH concentrations has been extensively studied in infertile women but there are only scarce data on AMH in non-infertile women. Our objective was to determine whether AMH concentrations influence the time necessary to conceive a live-born child - also called effective time to pregnancy (eTTP) - in a population of women who conceived naturally. We conducted an observational study between 2007 and 2009 in which we assessed eTTP retrospectively in 87 women who had delivered a live-born child and measured AMH in a frozen blood sample collected during the first trimester of pregnancy. The results of our study show, as expected, a decrease of AMH concentrations as age increases but no relationship between AMH and eTTP. In conclusion, our study results suggest AMH concentrations do not influence the time necessary to conceive a live-born child spontaneously and therefore speak against determining AMH in women who are not infertile for the purpose of predicting their chances of pregnancy. Our findings are concordant with previous reports describing AMH as a quantitative but not a qualitative marker of ovarian function that does therefore not reflect a woman's ability to become pregnant.

Measurement of hs-CRP is irrelevant to diagnose and stage endometriosis: prospective study of 834 patients.

OBJECTIVE: The pathogenesis of endometriosis is associated with an inflammatory process. Here, we assessed if the levels of high-sensitivity C-reactive protein (hs-CRP) in serum could constitute an effective method for detecting systemic inflammation during endometriosis. STUDY DESIGN: This was a prospective, laboratory-based study, which was carried out in a tertiary care university hospital. Patients with histologically proven endometriosis (n = 370) and unaffected women (n = 464) were enrolled from January 2005 through December 2009. We performed complete surgical excision of endometriotic lesions with pathological analysis. In addition, hs-CRP levels were determined through a particle-enhanced immunoturbidimetric method. The hs-CRP levels were measured in both controls and women with endometriosis according to the established surgical classifications of endometriosis: superficial peritoneal endometriosis, endometrioma, and deep infiltration endometriosis. Also, hs-CRP levels were evaluated according to hormonal treatment and menstrual cycle. RESULTS: The hs-CRP serum levels did not statistically differ between women with endometriosis and controls (median in ng/mL [range]: 0.82 [0.04-42.89] vs 0.9 [0.03-43.73], respectively; P = .599). Moreover, subgroup analysis revealed no difference among superficial peritoneal endometriosis, endometrioma, deep infiltration endometriosis, and controls: 0.8 (0.15-13.35), 0.81 (0.04-38.82), 0.83 (0.09-42.89), and 0.9 (0.03-43.73), respectively; P = .872. Furthermore, no effect was observed regarding hormonal treatment or menstrual cycle. CONCLUSION: Although endometriosis is an inflammatory disease, we failed to identify any systemic changes in hs-CRP serum levels. Therefore, hs-CRP analysis appears to be irrelevant to the diagnosis and staging of endometriosis.