Early GnRH-agonist therapy does not negatively impact the endometrial repair process or live birth rate.

Study objective: To investigate whether different timings of GnRH-a downregulation affected assisted reproductive outcomes in infertile women with moderate-to-severe intrauterine adhesions (IUAs) accompanied by adenomyosis. Design: A retrospective case series. Setting: An assisted reproductive technology center. Patients: The study reviewed 123 infertile women with moderate-to-severe IUAs accompanied by adenomyosis undergoing their first frozen-thawed embryo transfer (FET) cycles between January 2019 and December 2021. Measurements and main results: The majority of patients had moderate IUA (n=116, 94.31%). The average Basal uterine volume was 73.58 ± 36.50 cm3. The mean interval from operation to the first downregulation was 21.07 ± 18.02 days (range, 1-79 days). The mean duration of hormone replacement therapy (HRT) was 16.93 ± 6.29 days. The average endometrial thickness on the day before transfer was 10.83 ± 1.75 mm. A total of 70 women achieved clinical pregnancy (56.91%). Perinatal outcomes included live birth (n=47, 67.14%), early miscarriage (n=18, 25.71%), and late miscarriage (n=5, 7.14%). The time interval between uterine operation and the first downregulation was not a significant variable affecting live birth. Maternal age was the only risk factor associated with live birth (OR:0.89; 95% CI: 0.79-0.99, P=0.041). Conclusions: The earlier initiation of GnRH-a to suppress adenomyosis prior to endometrial preparation for frozen embryo transfer did not negatively impact repair of the endometrium after resection.

High progesterone levels on the day after HCG injection has no effect on clinical pregnancy outcomes in in vitro fertilization-embryo transfer.

Background: This study investigates the potential impact of high progesterone (P) level on the day following human chorionic gonadotropin (HCG) injection on the clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET). Methods: Retrospective analysis was conducted on 6418 cycles of IVF-ET performed at Liuzhou Maternal and Child Health Hospital between August 2020 to December 2021. Excluding cycles with progesterone levels ≥1.5ng/ml on HCG injection, a total of 781 cycles were identified according to the standard, and they were divided into five groups according to the progesterone level on the day after HCG: Group A: progesterone level < 2.5 ng/ml (n = 128); Group B: 2.5 ng/ml ≤ progesterone level < 3.5 ng/ml (n = 174); Group C: 3.5 ng/ml ≤ progesterone level < 4.5 ng/ml (n = 153); Group D: 4.5 ng/ml ≤ progesterone level < 5.5 ng/ml (n = 132); Group E progesterone level ≥5.5 ng/ml(n=194). Comparative analyses of clinical data, including general clinical data, and clinical pregnancy outcomes such as clinical pregnancy rate, miscarriage rate, and live birth rate were performed among these groups. Results: There were significant differences in estradiol levels on HCG injection, but there were no differences in available embryo rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Binary logistic regression analysis showed that there was no significant correlation between P level on the day after HCG injection and the live birth rate. Conclusion: Under the condition of low P level on HCG injection, high progesterone levels on the day after HCG injection does not affect the clinical pregnancy outcomes of IVF-ET.

[Live birth rates after breast cancer among women who desired a child]. / Naissances vivantes après cancer du sein parmi les femmes désirant un enfant.

INTRODUCTION: In France, the breast cancer is the most common cancer among women under the age of 40. From 38 to 70% of women have not fulfilled their parental plans at the time of diagnosis. The gonadotoxicity of the treatments and the follicular physiological decline linked to age can become an obstacle to this project. METHODS: Among the patients, 386 were treated for breast cancer at the Centre Georges-François-Leclerc in Dijon between January 2011 and December 2018 were identified. 192 patients aged under 39 met the inclusion criteria. We excluded metastatic cancers, cancer in situ and pregnant patients at diagnosis. A total of 124 patients agreed to participate in the study. The included patients filled out a self-questionnaire. Data were collected from the patient's electronic medical. The primary endpoint of this study was the live birth rate. RESULT: Among women who desired a child after breast cancer, the overall rate of live births was 36.2 % (21/58). Most achieved pregnancies were spontaneous (90.5 %). No factor was significantly associated with the absence of obtaining birth. Fertility was preserved by oocyte cryopreservation in 13.8 % of patients (17/124). The median time to conception in patients who received chemotherapy was 8 months [1.0-60.0] vs 2 months [1.0-7.0] in women who did not receive chemotherapy. DISCUSSION: The non-negligible proportion of live births following spontaneous pregnancy after breast cancer allows us to be reassuring for patients. However, the emergence of new chemotherapy protocols whose consequences on long-term gonadotoxicity are still not well known requires further studies and prompts the promotion of fertility preservation as a precautionary measure.

High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

PURPOSE: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). METHODS: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. RESULTS: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000-1999 pg/mL and 1000-1999 pg/mL versus 2000-2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999 pg/mL versus 3000-3999 pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9-1.04). CONCLUSION: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

[Analysis of related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes with mosaic embryo transfers].

Objective: To explore the related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes of mosaic embryo transfer in preimplantation genetic testing for aneuploidy (PGT-A) based on next generation sequencing (NGS) technology. Methods: A retrospective study was performed to analyze the clinical data of patients in 745 PGT-A cycles from January 2019 to May 2023 at Chongqing Health Center for Women and Children, including 2 850 blastocysts. The biopsy cells were tested using NGS technology, and the embryos were divided into three groups based on the test results, namely euploid embryos, aneuploid embryos and mosaic embryos. The influence of population characteristics and laboratory-related parameters on the detection rate of mosaic embryo were analyzed, and the pregnancy outcomes of 98 mosaic embryo transfer cycles and 486 euploid embryo transfer cycles were compared during the same period, including clinical pregnancy rate and live birth rate. Results: Among the embryos tested (n=2 850), the number and proportion of euploid embryos, aneuploid embryos and mosaic embryos were 1 489 (52.2%, 1 489/2 850), 917 (32.2%, 917/2 850) and 444 (15.6%, 444/2 850), respectively. Among mosaic embryos, 245 (55.2%, 245/444) were segmental mosaic embryos, 118 (26.6%, 118/444) were whole-chromosome mosaic embryos, and 81 (18.2%, 81/444) were complex mosaic embryos. NGS technology was performed in 4 genetic testing institutions and the detection rate of mosaic embryo fluctuated from 13.5% to 27.0%. The distributions of female age, level of anti-Müllerian hormone, PGT-A indications, ovulation-inducing treatments, gonadotropin (Gn) dosage, Gn days, inner cell mass grade, trophectoderm cell grade, genetic testing institutions and developmental stage of blastocyst were significantly different among the three groups (all P<0.05). Multi-factor analysis showed that the trophectoderm cell grade and genetic testing institutions were significantly related to the detection rate of mosaic embryo; compared with the trophectoderm cell graded as A, the detection rate of mosaic embryo was significantly increased in the trophectoderm cell graded as B-(OR=1.59, 95%CI: 1.04-2.44, P=0.033); compared with genetic testing institution a, the detection rate of mosaic embryo was significantly higher (OR=2.89, 95%CI: 2.10-3.98, P<0.001) in the testing institution c. The clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: 51.0% vs 65.2%, P=0.008; live birth rate: 39.4% vs 53.2%, P=0.017). After adjustment for age, PGT-A indications, trophectoderm cell grade and days of embryo culture in vitro, the clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: OR=0.52, 95%CI: 0.32-0.83, P=0.007; live birth rate: OR=0.50, 95%CI: 0.31-0.83, P=0.007). Conclusions: The trophectoderm cell grade and genetic testing institutions are related to the detection rate of mosaic embryo. Compared with euploid embryos transfer, the clinical pregnancy rate and live birth rate with mosaic embryos transfer are significantly reduced. For infertile couple without euploid embryos, transplantable mosaic embryos could be recommended according to the mosaic ratio and mosaic type in genetic counseling to obtain the optimal pregnancy outcome.

Folate and vitamin B12 status and predicted neural tube defects risk among nonpregnant women of reproductive age from the Malawi National Micronutrient Survey, 2015-2016.

BACKGROUND: Maternal folate and vitamin B12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B12 status among women of reproductive age (WRA) in Malawi. OBJECTIVE: We assessed folate and vitamin B12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant. METHODS: Using data from the cross-sectional, nationally representative 2015-2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15-49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design. RESULTS: Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education. CONCLUSIONS: These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B12 nutrition among Malawian WRA.

Biomarkers identification in follicular fluid in relation to live birth in in vitro fertilization of women with polycystic ovary syndrome in different subtypes by using UPLC-MS method.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common infertility disorder which affects reproductive-aged women. However, metabolic change profiles of follicular fluid (FF) in lean and obese women diagnosed with and without PCOS remains unclear. METHODS: 95 infertile women were divided into four subgroups: LC (lean control), OC (overweight control), LP (lean PCOS), and OP (overweight PCOS). The FF samples were collected during oocyte retrieval and assayed by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) metabolomics. RESULTS: A total of 236 metabolites were identified by metabolic analysis. The pathway enrichment analysis revealed that the glycerophospholipid metabolism (impact = 0.11182), ether lipid metabolism (impact = 0.14458), and primary bile acid biosynthesis (impact = 0.03267) were related to metabolic pathway between PCOS and control. Correlation analyses showed that epitestosterone sulfate was found positively correlated with fertilization rate in PCOS, while falcarindione, lucidone C. and notoginsenoside I was found to be negatively correlated. The combined four biomarkers including lucidone C, epitestosterone sulfate, falcarindione, and notoginsenoside I was better in predicting live birth rate, with AUC of 0.779. CONCLUSION: The follicular fluid of women with PCOS showed unique metabolic characteristics. Our study provides better identification of PCOS follicular fluid metabolic dynamics, which may serve as potential biomarkers of live birth.

Successful live birth of thin endometrium: A case report.

RATIONALE: The success of pregnancy depends on various factors, with the endometrial receptivity being a crucial component. Endometrial thickness (EMT) serves as a direct indicator for assessing endometrial receptivity. Previous studies have suggested that a thin endometrium is associated with lower pregnancy rates, especially in patients with an EMT of less than 4 mm. Even in assisted reproductive technology cycles with high success rates, clinical pregnancy cases in patients with such thin endometrium are reported to be very few, let alone in natural conception cycles. Therefore, a thin endometrium poses significant challenges for infertility patients. In this study, patients with an extremely thin endometrium were able to achieve clinical pregnancy and successful live births through natural conception, highlighting the possibility of success even in challenging cases. PATIENT CONCERNS: The patient presented with polycystic ovary syndrome and ovulation disorders. She underwent a natural cycle of letrozole-induced ovulation. On the day of the human chorionic gonadotropin trigger, she had an EMT of 3.8 mm. DIAGNOSES: Polycystic ovary syndrome, ovulation disorders, thin endometrium. INTERVENTIONS: The patient received medications including Progynova, Aspirin, and Dydrogesterone. OUTCOMES: The patient achieved spontaneous conception and subsequently had a live birth. LESSONS: This case report underscores the significance of managing a thin endometrium during letrozole-induced ovulation. While EMT is traditionally pivotal for predicting embryo implantation success, our findings indicate that endometrial receptivity extends beyond thickness alone. Factors such as endometrial morphology, type, and blood supply play crucial roles. Successful pregnancies with a 3.8 mm EMT are rare, making this case a beacon of hope for such patients. It highlights that, with appropriate interventions, successful pregnancies remain attainable. For those with a thin endometrium, emphasis should extend beyond thickness, addressing ways to enhance both endometrial blood supply and morphology for improved pregnancy rates.

Effects of hysteroscopic septum incision versus expectant management on IVF outcomes in women with complete septate uterus: a retrospective study.

OBJECTIVE: This retrospective study aimed to assess the impact of hysteroscopic septum incision on in vitro fertilization (IVF) outcomes among infertile women diagnosed with a complete septate uterus and no history of recurrent pregnancy loss. METHODS: The study was conducted at a tertiary reproductive center affiliated with a university hospital and involved 78 women with a complete septate uterus. Among them, 34 women underwent hysteroscopic septum incision, while 44 women opted for expectant management. The primary outcome measure was the live birth rate, while secondary outcomes included clinical pregnancy rate, preterm birth rate, miscarriage rate, and ongoing pregnancy rate. RESULTS: Women who underwent hysteroscopic septum incision demonstrated a comparable likelihood of achieving a live birth compared to those managed expectantly (25% vs. 25%, Relative Risk (RR): 1.000, 95% Confidence Interval (CI): 0.822 to 1.216). No preterm births occurred in either group. The clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate showed no significant differences between the surgical group and the expectant management group. Subgroup analyses based on the type of embryo transferred also revealed no significant differences in outcomes. CONCLUSIONS: Hysteroscopic septum incision does not appear to yield improved IVF outcomes compared to expectant management in infertile women with a complete septate uterus and no history of recurrent pregnancy loss.

Maternal mortality in the United States: are the high and rising rates due to changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance?

BACKGROUND: National Vital Statistics System reports show that maternal mortality rates in the United States have nearly doubled, from 17.4 in 2018 to 32.9 per 100,000 live births in 2021. However, these high and rising rates could reflect issues unrelated to obstetrical factors, such as changes in maternal medical conditions or maternal mortality surveillance (eg, due to introduction of the pregnancy checkbox). OBJECTIVE: This study aimed to assess if the high and rising rates of maternal mortality in the United States reflect changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance. STUDY DESIGN: The study was based on all deaths in the United States from 1999 to 2021. Maternal deaths were identified using the following 2 approaches: (1) per National Vital Statistics System methodology, as deaths in pregnancy or in the postpartum period, including deaths identified solely because of a positive pregnancy checkbox, and (2) under an alternative formulation, as deaths in pregnancy or in the postpartum period, with at least 1 mention of pregnancy among the multiple causes of death on the death certificate. The frequencies of major cause-of-death categories among deaths of female patients aged 15 to 44 years, maternal deaths, deaths due to obstetrical causes (ie, direct obstetrical deaths), and deaths due to maternal medical conditions aggravated by pregnancy or its management (ie, indirect obstetrical deaths) were quantified. RESULTS: Maternal deaths, per National Vital Statistics System methodology, increased by 144% (95% confidence interval, 130-159) from 9.65 in 1999-2002 (n=1550) to 23.6 per 100,000 live births in 2018-2021 (n=3489), with increases occurring among all race and ethnicity groups. Direct obstetrical deaths increased from 8.41 in 1999-2002 to 14.1 per 100,000 live births in 2018-2021, whereas indirect obstetrical deaths increased from 1.24 to 9.41 per 100,000 live births: 38% of direct obstetrical deaths and 87% of indirect obstetrical deaths in 2018-2021 were identified because of a positive pregnancy checkbox. The pregnancy checkbox was associated with increases in less specific and incidental causes of death. For example, maternal deaths with malignant neoplasms listed as a multiple cause of death increased 46-fold from 0.03 in 1999-2002 to 1.42 per 100,000 live births in 2018-2021. Under the alternative formulation, the maternal mortality rate was 10.2 in 1999-2002 and 10.4 per 100,000 live births in 2018-2021; deaths from direct obstetrical causes decreased from 7.05 to 5.82 per 100,000 live births. Deaths due to preeclampsia, eclampsia, postpartum hemorrhage, puerperal sepsis, venous complications, and embolism decreased, whereas deaths due to adherent placenta, renal and unspecified causes, cardiomyopathy, and preexisting hypertension increased. Maternal mortality increased among non-Hispanic White women and decreased among non-Hispanic Black and Hispanic women. However, rates were disproportionately higher among non-Hispanic Black women, with large disparities evident in several causes of death (eg, cardiomyopathy). CONCLUSION: The high and rising rates of maternal mortality in the United States are a consequence of changes in maternal mortality surveillance, with reliance on the pregnancy checkbox leading to an increase in misclassified maternal deaths. Identifying maternal deaths by requiring mention of pregnancy among the multiple causes of death shows lower, stable maternal mortality rates and declines in maternal deaths from direct obstetrical causes.

Age and dual trigger were found to be significant predictors of live birth in POSEIDON group 3 and 4 women treated with the GnRH antagonist protocol: a retrospective cohort study.

OBJECTIVE: Despite recent advancements in assisted reproductive technology (ART), the effective management of patients with poor ovarian response (POR) remains a formidable challenge. While various treatment strategies and predictors of live births have been documented to provide guidance to fertility specialists in managing poor responders, research efforts have predominantly encompassed all POSEIDON groups. In this study, our objective was to analyze the factors correlated with live births (LB) within a subset of the POSEIDON groups, with a particular focus on POSEIDON groups 3 and 4. PATIENTS AND METHODS: Charts of 406 patients belonging to POSEIDON groups 3 and 4 who underwent ART treatment at a university-affiliated infertility clinic following a gonadotropin-releasing hormone (GnRH) antagonist cycle between January 2016 and December 2021 were analyzed. Clinically significant factors associated with live births were incorporated into a logistic regression model for multivariate analysis to ascertain independent predictors of LB. Additionally, a receiver operating characteristic (ROC) curve analysis was conducted to establish the optimal cut-off values. RESULTS: Live births were achieved in 48 cycles (8.7%). Female age (OR, 0.930; 95% CI: 0.874-0.991; p < 0.024), baseline serum luteinizing hormone (LH) levels (OR, 0.854; 95% CI: 0.741-0.984; p < 0.029), and dual triggers (OR, 4.004; 95% CI: 1.290-12.426; p < 0.016) were identified as independent factors associated with LB following multivariate logistic regression analysis. The optimal age cut-off was determined to be 33 years, with a sensitivity of 70.8% and specificity of 75%. CONCLUSIONS: Younger age, lower baseline serum LH levels, and dual-trigger administration appear to enhance the likelihood of live birth in POSEIDON groups 3 and 4 following treatments with the GnRH antagonist protocol.

Natural proliferative phase frozen embryo transfer-a new approach which may facilitate scheduling without hindering pregnancy outcomes.

STUDY QUESTION: How does a natural proliferative phase (NPP) strategy for frozen embryo transfer (FET) compare with the conventional artificial (AC) and natural (NC) endometrial preparation protocols in terms of live birth rates (LBR)? SUMMARY ANSWER: This study supports the hypothesis that, just as for NC, NPP-FET may be a superior alternative to AC in terms of LBR. WHAT IS KNOWN ALREADY: Although FETs are increasing worldwide, the optimal FET protocol is still largely controversial. Despite recent evidence supporting a possibly higher efficacy and safety of NC FETs, their widespread use is limited by the difficulties encountered during cycle monitoring and scheduling. STUDY DESIGN, SIZE, DURATION: In this single center retrospective cohort study, we describe the NPP-FET protocol, in which vaginal progesterone is initiated during the proliferative phase as soon as an endometrium with a thickness of at least 7 mm is identified and ovulation is ruled out, regardless of mean diameter of the dominant follicle. PARTICIPANTS/MATERIALS, SETTING, METHODS: For comparison, we considered all blastocyst stage FET cycles preformed at a private infertility center between January 2010 and June 2022, subdivided according to the following subgroups of endometrial preparation: AC, NPP, and NC. We performed multivariable generalized estimating equations regression analysis to account for the following potential confounding variables: oocyte age at retrieval, oocyte source (autologous without preimplantation genetic testing for aneuploidies (PGT-A) versus autologous with PGT-A versus donated), number of oocytes retrieved/donated, embryo developmental stage (Day 5 versus Day 6), number of embryos transferred, quality of the best embryo transferred, and year of treatment. The main outcome measure was LBR. The secondary outcomes included hCG positive, clinical pregnancy and miscarriage rates, and the following perinatal outcomes: first trimester bleeding, second/third trimester bleeding, preterm rupture of membranes, gestational diabetes, gestational hypertensive disorders (GHD), and gestational age at delivery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 5791 FET cycles were included in this analysis (2226 AC, 349 NPP, and 3216 NC). The LBR for FET was lower in the AC subgroup when compared to the NPP and NC (38.4%, 49.1%, and 45.2%, respectively; P < 0.01 AC versus NPP and AC versus NC). The rates of miscarriage were also lower in the NPP and NC subgroups when compared to AC (19.7%, 25.0%, and 34.9%, respectively; P < 0.01 NPP versus AC and NC versus AC). Considering perinatal outcomes, NPP-FET and NC were associated with a significantly lower first trimester bleeding compared to AC (17.3%, 14.7%, and 37.6%, respectively; P < 0.01 NPP versus AC and NC versus AC). Additionally, NC was associated with a lower rate of GHD when compared with AC (8.6% versus 14.5%, P < 0.01), while the rate following NPP-FET was 9.4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design. Moreover, there was also a low number of patients in the NPP subgroup, which may have led the study to be underpowered to detect clinically relevant differences between the subgroups. WIDER IMPLICATIONS OF THE FINDINGS: Our study posits that the NPP-FET protocol may be an effective and safe alternative to both NC and AC, while still allowing for enhanced practicality in patient follow-up and FET scheduling. Further investigation on NPP-FET is warranted, with prospective studies including a larger and more homogeneous subsets of patients. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the IVI-RMA-Lisbon (2008-LIS-053-CG). The authors did not receive any funding for this study. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123 987 patients.

STUDY QUESTION: What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation? SUMMARY ANSWER: The fourth and fifth euploid blastocyst transfers resulted in similar live birth rates of 40% and 53.3%, respectively, culminating in a cumulative live birth rate of 98.1% (95% CI = 96.5-99.6%) after five euploid blastocyst transfers. WHAT IS KNOWN ALREADY: The first three euploid blastocysts have similar implantation and live birth rates and provide a cumulative live birth rate of 92.6%. STUDY DESIGN, SIZE, DURATION: An international multi-center retrospective study was conducted at 25 individual clinics. The study period spanned between January 2012 and December 2022. A total of 123 987 patients with a total of 64 572 euploid blastocyst transfers were screened for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with a history of any embryo transfer at another clinic, history of any unscreened embryo transfer at participating clinics, parental karyotype abnormalities, the use of donor oocytes or a gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital uterine anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior to initiating of progesterone, use of testicular sperm due to non-obstructive azoospermia in the male partner, transfer of an embryo with a reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles for monogenic disorders, or structural chromosome rearrangements were excluded. Ovarian stimulation protocols and embryology laboratory procedures including trophectoderm biopsy followed the usual practice of each center. The ploidy status of blastocysts was determined with comprehensive chromosome screening. Endometrial preparation protocols followed the usual practice of participating centers and included programmed cycles, natural or modified natural cycles. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 105 (0.085% of the total population) patients met the criteria and underwent at least one additional euploid blastocyst transfer after failing to achieve a positive pregnancy test with three consecutive euploid blastocyst transfers. Outcomes of the fourth and fifth euploid blastocyst transfers were similar across participating centers. Overall, the live birth rate was similar with the fourth and fifth euploid blastocysts (40% vs 53.3%, relative risk = 1.33, 95% CI = 0.93-1.9, P value = 0.14). Sensitivity analyses excluding blastocysts biopsied on Day 7 postfertilization, women with a BMI >30 kg/m2, cycles using non-ejaculate or donor sperm, double-embryo transfer cycles, and cycles in which the day of embryo transfer was modified due to endometrial receptivity assay test result yielded similar results. Where data were available, the fourth euploid blastocyst had similar live birth rate with the first one (relative risk = 0.84, 95% CI = 0.58-1.21, P = 0.29). The cumulative live birth rate after five euploid blastocyst transfers was 98.1% (95% CI = 96.5-99.6%). LIMITATIONS, REASONS FOR CAUTION: Retrospective design has its own inherent limitations. Patients continuing with a further euploid embryo transfer and patients dropping out from treatment after three failed euploid transfers can be systematically different, perhaps with regard to ovarian reserve or economic status. WIDER IMPLICATION OF THE FINDINGS: Implantation failure seems to be mainly due to embryonic factors. Given the stable and high live birth rates up to five euploid blastocysts, unexplained recurrent implantation failure should have a prevalence of <2%. Proceeding with another embryo transfer can be the best next step once a known etiology for implantation failure is ruled out. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histologic disease activity. METHODS: Nationwide IBD cohort of Swedish women aged 15 to 44 years. We examined fertility rates during periods with vs without histologic inflammation (n = 21,046; follow-up, 1990-2016) and during periods with vs without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n = 24,995; follow-up, 2006-2020). Accounting for sociodemographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live births conceived during 12-month periods of histologic inflammation (vs histologic remission) and 3-month periods of clinically active IBD (vs quiescent IBD). RESULTS: During periods with vs without histologic inflammation, there were 6.35 (95% confidence interval [CI], 5.98-6.73) and 7.09 (95% CI, 6.48-7.70) live births conceived per 100 person-years of follow-up, respectively, or 1 fewer child per 14 women with 10 years of histologic inflammation (aFRR, 0.90; 95% CI, 0.81-1.00). In women with histologic inflammation, fertility was similarly reduced in ulcerative colitis (UC) (aFRR, 0.89 [95% CI, 0.78-1.02]) and Crohn's disease (CD) (aFRR, 0.86 [95% CI, 0.72-1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95% CI, 0.72-0.79) or 1 fewer child per 6 women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR, 0.75 [95% CI, 0.70-0.81]) and CD (aFRR, 0.76 [95% CI, 0.70-0.82]). Finally, among women with clinically quiescent IBD, histologic inflammation (vs histologic remission) was associated with reduced fertility (aFRR, 0.85 [95% CI, 0.73-0.98]). CONCLUSIONS: An association between histologic and clinical activity and reduced female fertility in CD and UC was found. Notably, histologic inflammation was also linked to reduced fertility in women with clinically quiescent IBD.

Does surgery for colorectal endometriosis prior to IVF±ICSI have an impact on cumulative live birth rates?

RESEARCH QUESTION: Does colorectal endometriosis surgery prior to IVF ± intracytoplasmic sperm injection (ICSI) impact cumulative live birth rates? DESIGN: This retrospective, monocentric study (Lille University Hospital) was conducted between 1 January 2007 and 31 December 2018. Two groups of patients from the JFIV database were included: a group undergoing IVF±ICSI alone (120 patients, 215 oocyte retrievals), and a group undergoing surgery and then IVF±ICSI (69 patients, 109 oocyte retrievals). The mode of management was decided after a multidisciplinary team meeting. Different criteria such as age (cut-off 35 years), anti-Müllerian hormone concentration (cut off 2 ng/ml), imaging results and the patient's symptomatology were considered: the most symptomatic patients underwent surgery prior to IVF±ICSI. The cumulative clinical pregnancy and live birth rates obtained after four IVF attempts were estimated and compared between the two groups using competing risk survival methods. RESULTS: The cumulative live birth rates after four IVF attempts in the two groups were not statistically significantly different (50.8% in the IVF±ICSI group versus 52.2% in the surgery followed by IVF±ICSI group, P = 0.43). The results for the cumulative clinical pregnancy rates were the same (56.7% in the IVF±ICSI group versus 58% in the surgery followed by IVF±ICSI group, P = 0.47). CONCLUSION: The study shows that cumulative live birth and pregnancy rates were similar in infertile patients with colorectal endometriosis who underwent IVF±ICSI either with or without prior colorectal endometriosis surgery.

CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Association between proliferative-to-secretory endometrial compaction and pregnancy outcomes after embryo transfer: a systematic review and meta-analysis.

STUDY QUESTION: Does the change in endometrial thickness (EMT) from the end of the follicular/estrogen phase to the day of embryo transfer (ET) determine subsequent pregnancy outcomes? SUMMARY ANSWER: Endometrial compaction from the late-proliferative to secretory phase is not associated with live birth rate (LBR) and other pregnancy outcomes. WHAT IS KNOWN ALREADY: Endometrial compaction has been suggested to be indicative of endometrial responsiveness to progesterone, and its association with ET outcome has been investigated but is controversial. STUDY DESIGN, SIZE, DURATION: A systematic review with meta-analysis was carried out. PubMed, EMBASE, and Web of Science were searched to identify relevant studies from inception to 18 November 2022. The reference lists of included studies were also manually screened for any additional publications. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort studies comparing ET pregnancy outcomes between patients with and without endometrial compaction were included. A review of the studies for inclusion, data extraction, and quality assessment was performed by two independent reviewers. The effect size was synthesized as odds ratio (OR) with 95% CI using a random-effects model. Heterogeneity and publication bias were assessed by the I2 statistic and Egger's test, respectively. The primary outcome was LBR. Secondary outcomes included biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), miscarriage rate (MR), ongoing pregnancy rate (OPR), and ectopic pregnancy rate (EPR). MAIN RESULTS AND THE ROLE OF CHANCE: Seventeen cohort studies involving 18 973 ET cycles fulfilled the eligibility criteria. The pooled results revealed that there were no significant differences between endometrial compaction and non-compaction groups in LBR (crude OR (cOR) = 0.95, 95% CI 0.87-1.04; I2 = 0%; adjusted OR (aOR) = 1.02, 95% CI 0.87-1.19, I2 = 79%), BPR (cOR = 0.93, 95% CI 0.81-1.06; I2 = 0%; aOR = 0.88, 95% CI 0.75-1.03, I2 = 0%), CPR (cOR = 0.98, 95% CI 0.81-1.18; I2 = 70%; aOR = 0.86, 95% CI 0.72-1.02, I2 = 13%), MR (cOR = 1.09, 95% CI 0.90-1.32; I2 = 0%; aOR = 0.91, 95% CI 0.64-1.31; I2 = 0%), and EPR (cOR = 0.70, 95% CI 0.31-1.61; I2 = 61%). The OPR was marginally higher in crude analysis (cOR = 1.48, 95% CI 1.01-2.16; I2 = 81%) among women with compacted endometrium, but was not evident in adjusted results (aOR = 1.36, 95% CI 0.86-2.14; I2 = 84%). Consistently, the pooled estimate of LBR remained comparable in further subgroup and sensitivity analyses according to the degree of compaction (0%, 5%, 10%, 15%, or 20%), type of ET (fresh, frozen, or euploid only), and endometrial preparation protocol (natural or artificial). No publication bias was observed based on Egger's test. LIMITATIONS, REASONS FOR CAUTION: Although the number of included studies is sufficient, data on certain measures, such as EPR, are limited. The inherent bias and residual confounding were also inevitable owing to the observational study design. Furthermore, inconsistent definitions of pregnancy outcomes may affect the accuracy of our pooled analysis. WIDER IMPLICATIONS OF THE FINDINGS: Given the lack of prognostic value, assessing endometrial compaction or repeated EMT measurement on the day of ET may not be necessary or warranted. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Natural Science Foundation of Jiangxi Province (20224BAB216025), National Natural Science Foundation of China (82260315), and Central Funds Guiding the Local Science and Technology Development (20221ZDG020071). The authors have no conflicts of interest to declare. REGISTRATION NUMBER: CRD42022384539 (PROSPERO).

Outpatient hysteroscopy impact on subsequent assisted reproductive technology: a systematic review and meta-analysis in patients with normal transvaginal sonography or hysterosalpingography images.

BACKGROUND: Standard management for intrauterine lesions typically involves initial imaging followed by operative hysteroscopy for suspicious findings. However, the efficacy of routine outpatient hysteroscopy in women undergoing assisted reproductive technology (ART) remains uncertain due to a lack of decisive high-quality evidence. This study aimed to determine whether outpatient hysteroscopy is beneficial for infertile women who have unremarkable imaging results prior to undergoing ART. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines, incorporating data up to May 31, 2023, from databases such as PubMed, Embase, and the Cochrane Library. The primary outcome assessed was the live birth rate, with secondary outcomes including chemical pregnancy, clinical pregnancy rates, and miscarriage rates. Statistical analysis involved calculating risk ratios with 95% confidence intervals and assessing heterogeneity with the I2 statistic. RESULTS: The analysis included ten randomized control trials. Receiving outpatient hysteroscopy before undergoing ART was associated with increased live birth (RR 1.22, 95% CI 1.03-1.45, I2 61%) and clinical pregnancy rate (RR 1.27 95% CI 1.10-1.47, I2 53%). Miscarriage rates did not differ significantly (RR 1.25, CI 0.90-1.76, I2 50%). Subgroup analyses did not show a significant difference in clinical pregnancy rates when comparing normal versus abnormal hysteroscopic findings (RR 1.01, CI 0.78-1.32, I2 38%). We analyzed data using both intention-to-treat and per-protocol approaches, and our findings were consistent across both analytical methods. CONCLUSIONS: Office hysteroscopy may enhance live birth and clinical pregnancy rates in infertile women undergoing ART, even when previous imaging studies show no apparent intrauterine lesions. Treating lesions not detected by imaging may improve ART outcomes. The most commonly missed lesions are endometrial polyps, submucosal fibroids and endometritis, which are all known to affect ART success rates. The findings suggested that hysteroscopy, given its diagnostic accuracy and patient tolerability, should be considered in the management of infertility. DATABASE REGISTRATION: The study was registered in the International Prospective Register of Systemic Review database (CRD42023476403).

Basal characteristics of patients who responded to Ovarian Fragmentation for Follicular Activation (OFFA) or In Vitro Activation (IVA): a systematic review and meta-analysis.

A systematic review and meta-analysis were performed to identify if there is a subset of patients with POI who are more likely to show follicular growth after ovarian fragmentation for follicular activation (OFFA) or in vitro activation (IVA). Five studies met inclusion criteria for meta-analysis with a total of 164 patients. Forty-three patients showed follicle development (26.21%). Of those, the pregnancy rate was 35.58% (11/43) and the live birth rate was 20.93% (9/43). Our meta-analysis showed that age was not associated with follicle growth. However, lower baseline FSH, lower duration of amenorrhea/diagnosis, and presence of follicles remaining in biopsy were statistically significant for follicle development. Patients with basal characteristics mentioned before may have more chances to show follicle growth after OFFA or IVA. Taking into account that approximately 20% of patients with follicle growth had live birth, these results are very promising. Given the overall certainty of evidence, future studies are needed to confirm said results.

Geographic Differences in Preconception Health Indicators Among Ohio Women Who Delivered Live Births, 2019-2021.

To determine whether geographic differences in preconception health indicators exist among Ohio women with live births, we analyzed 9 indicators from the 2019-2021 Ohio Pregnancy Assessment Survey (N = 14,377) by county type. Appalachian women reported lower rates of folic acid intake and higher rates of depression than women in other counties. Appalachian and rural non-Appalachian women most often reported cigarette use. Suburban women reported lower rates of diabetes, hypertension, and unwanted pregnancy than women in other counties. Preconception health differences by residence location suggest a need to customize prevention efforts by region to improve health outcomes, particularly in regions with persistent health disparities.