Local testosterone regulation is critical for male fertility but poorly understood. We show that loss of CCDC117 triggers testosterone elevation despite lower luteinizing hormone levels, revealing a gonadotropin-independent compensatory mechanism that preserves fertility in smaller testes. AbstractThe local regulation of testicular steroidogenesis is essential for male fertility but remains incompletely understood. Here, we identify the testis-enriched protein CCDC117 as a critical, local brake on testicular testosterone production. Ccdc117 knockout mice exhibited a paradoxical phenotype: significant reduced testis size (∼21% reduction in weight) accompanied by diminished seminiferous tubule area, yet displaying fully preserved sperm production and near-normal fertility. Mechanistically, loss of CCDC117 triggers a cell-autonomous, compensatory upregulation of the steroidogenic pathway specifically in Leydig cells, leading to a 2-fold increase in serum testosterone without a rise in luteinizing hormone. Consistently, intratesticular testosterone levels were significantly elevated (∼1.5-fold), directly confirming enhanced local androgen production. This gonadotropin-independent hyperandrogenemia likely supports the maintenance of normal spermatogenic cell numbers within the compromised tubules, facilitating higher-efficiency spermatogenesis that ultimately preserves male fertility in the context of a smaller testis. Collectively, these findings demonstrate that CCDC117 deficiency releases a constitutive brake on Leydig cell steroidogenesis. The resulting compensatory hyperandrogenemia maintains reproductive function under structural compromise, thus uncovering a previously unrecognized local mechanism that ensures reproductive resilience.

BACKGROUND:The influence of paternal Hepatitis B virus infection on reproductive outcomes after in vitro fertilization or intracytoplasmic sperm injection is still debated. While differences in sperm-oocyte interaction duration and intensity between in vitro fertilization and intracytoplasmic sperm injection may lead to divergent viral exposure effects. Nevertheless, research specifically examining these differences remains limited. OBJECTIVES:To evaluate how various insemination techniques influence the effects of paternal Hepatitis B virus infection on reproductive outcomes in couples during in vitro fertilization/intracytoplasmic sperm injection treatments. MATERIAL AND METHODS:This retrospective study analyzed 37,088 initial frozen-thawed embryo transfer cycles among women without Hepatitis B virus infection from February 2007 to August 2023. Patients were grouped into two categories based on paternal Hepatitis B virus surface antigen status: paternal Hepatitis B virus surface antigen positive (Hepatitis B virus surface antigen [+]) and negative (Hepatitis B virus surface antigen [-]) categories. Further stratified analyses were performed according to the insemination method. The primary endpoints were measures of pregnancy and neonatal results. An analysis using logistic regression was conducted to explore the independent link between paternal Hepatitis B virus infection and the specified outcomes. RESULTS:In in vitro fertilization-derived embryos, paternal Hepatitis B virus infection was significantly associated with an elevated risk of miscarriage (adjusted odds ratio 1.55, 95% confidence interval 1.22-1.96), small for gestational age (adjusted odds ratio 1.70, 95% confidence interval 1.12-2.59), and very small for gestational age (adjusted odds ratio 3.07, 95% confidence interval 1.64-5.76) by comparison with controls. No such associations occurred with intracytoplasmic sperm injection-derived embryos. DISCUSSION:Prior studies have shown inconsistent findings on the effects of paternal Hepatitis B virus infection on these outcomes. This study provides evidence that paternal infection with the Hepatitis B virus independently elevates the risks of miscarriage, small for gestational age, and very small for gestational age births following in in vitro fertilization, but not intracytoplasmic sperm injection. This discrepancy might be due to differences in the extent and duration of oocyte exposure to the Hepatitis B virus. CONCLUSIONS:Male Hepatitis B virus infection independently increases the risk of miscarriages and the birth of small for gestational age and very small for gestational age infants after in vitro fertilization embryo transfer, but not after intracytoplasmic sperm injection.

Early embryonic arrest is one of the reasons for the recurrent IVF/ICSI failures. We aimed to identify pathogenic mutations in female infertility patients with early embryonic arrest. Whole-exome sequencing was performed in the affected patients. Sanger sequencing was used on patients and their families to confirm the identified mutations. Wild-type and mutant plasmids were constructed and transfected into HeLa cells to investigate the functional effect of the identified mutations. We identified three novel homozygous mutations of NLRP2 (p.Arg81*, p.Lys312del, and p.Val316Ala) and compound heterozygous mutations with a novel frameshift mutation and a novel missense mutation of NLRP7 (p.Gln315Arg fs*5 and p.Ile830Thr) in the affected individuals with early embryonic arrest. Western blot in HeLa cells showed the mutations caused a significant decrease in NLRP2 and NLRP7 to a varying degree, which impaired the stability of the proteins. Immunofluorescent staining showed some mutations altered the localization of NLRP2 and NLRP7. This study identified novel mutations in NLRP2 and NLRP7, expanding the mutational and phenotypic spectrum of NLRP2 and NLRP7. Our findings also establish the foundation for genetic diagnosis in recurrent IVF/ICSI failure patients with early embryonic arrest.

Endometriosis (EM) results in pelvic adhesions and chronic inflammation, which significantly reduce embryo implantation and the clinical pregnancy rates of in vitro fertilization (IVF), affecting 190 million women worldwide. Traditional hormonal and surgical treatments alter ovarian and endometrial function, thereby hindering IVF. An urgent need exists for a localized treatment strategy that does not interfere with IVF procedures, aiming to enhance endometrial receptivity. To address this, we developed an innovative localized drug delivery system that simultaneously targets immune dysregulation and enhances endometrial function. This study reports a dual‐drug delivery system based on poly(N‐isopropylacrylamide) (PNIPAM) combined with nanocrystalline cellulose (CNC) for the local release of levonorgestrel (LNG) and botropase (BTP) to reprogram uterine natural killer cells and treat EM, overcoming previous drawbacks. The experimental results confirm stable CNC and PNIPAM structures and controlled the release of the composite drug. At concentrations of 0.5 mg/L LNG and 100 mg/L BTP, the release system achieved the highest CD16–/CD16+ ratio and the most pronounced upregulation of autophagy‐related molecules in uNK cells in our in vitro assays, indicating a shift in uNK cells toward an immune‐tolerant state. In a mouse model of EM, the CNC–PNIPAM drug delivery system significantly improve endometrial receptivity. The CNC–PNIPAM drug delivery system demonstrates the medical potential of the local release of composite drugs, offering a new immunomodulatory approach for the treatment of EM and broader medical applications.

To investigate whether single frozen-thawed blastocyst transfers derived from poor-grade Day 3 embryos influence neonatal outcomes. This retrospective cohort study conducted in a tertiary academic medical center included all the live-born singletons (n = 3156) in vitrified-warmed single blastocyst transfer cycles from January 2013 to November 2023, which were divided into the poor-grade group (n = 2432) and the high-grade group (n = 724) based on the embryo grade on Day 3. Propensity score matching (PSM) analysis and multivariate regression analysis were used to explore the association between the embryo grade on Day 3 and neonatal outcomes. After PSM, the baseline characteristics were all comparable between the two groups. There was a significant gender difference between the two groups (P = 0.004), while there were no differences in the mode of delivery, very preterm birth, preterm birth, very low birth weight, low birth weight, macrosomia, small for gestational age, large for gestational age, or congenital malformations (P > 0.05). After multivariate regression analysis, it was shown that the proportion of male neonates born through blastocyst transfer derived from poor-grade Day 3 embryos was considerably higher (aOR 0.710, 95

RESEARCH QUESTION:Can polarized light microscopy (PLM) spindle phenotypes predict the developmental potential of non-pronuclear (0PN) zygotes? DESIGN:Retrospective observational study including 1266 0PN zygotes and 69,383 two-pronuclei (2PN) zygotes from patients undergoing IVF and embryo transfer treatments in a reproductive centre affiliated to a university hospital from June 2021 to November 2024. Phenotypic observations were obtained through PLM; all 0PN zygotes were categorized into four distinct groups: adjacent dual spindles (AD-SP); separate dual spindles (SD-SP); mono-spindle (M-SP) and no spindle (N-SP). Logistic regression assessed the effect of these PLM phenotypes on embryological outcomes, considering parental and treatment factors, and evaluated the effects of rescue artificial oocyte activation or rescue ICSI on these outcomes. RESULTS:Cleavage rates were significantly lower in AD-SP (adjusted odds ratio [aOR] 0.22; P < 0.001), SD-SP (aOR 0.03; P < 0.001), M-SP (aOR 0.02; P < 0.001), and N-SP (aOR 0.02; P < 0.001) categories compared with 2PN zygotes. The rates of four or more cells at day 3 (aOR 1.97; P = 0.041), six or more cells on day 3 (aOR 1.60; P = 0.012) and good-quality embryos at day 3 (aOR 1.58; P = 0.008) were significantly higher in AD-SP categories compared with 2PN zygotes. Blastocyst formation rates of day-3 poor-quality embryos (aOR 1.31; P = 0.351) was comparable between 2PN zygotes and 0PN zygotes with AD-SP. CONCLUSIONS:Four prominent phenotypes of 0PN zygotes were identified based on PLM, along with their corresponding embryonic outcomes. Notably, 0PN zygotes with AD-SP had embryonic outcomes similar to those of 2PN zygotes, except for cleavage rate, and demonstrated superior developmental potential compared with other phenotypes.

Telomere length (TL) is important for maintaining the individual health of a species. Recent studies shows that in vitro fertilization therapy can drastically reduce TL in offspring, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD+-dependent epigenetic regulator that has recently been found to play an important role in maintaining telomere stability. Here, we report that NAD+ deficiency in in vitro-cultured blastocysts impairs Sirt6 function, triggering telomere shortening of the inner cell mass and possibly affecting newborns. This phenotype could be effectively mitigated by supplementation with nicotinamide mononucleotide (NAD+ precursor) during in vitro culture, while it could not be achieved in Sirt6 conditional knockout embryos. mtROS accumulation and epigenetic modifications may also be involved in this process. Our results reveal the mechanism by which in vitro culture induces telomere shortening in preimplantation embryos, providing a potential target for improving in vitro culture conditions.

In brief: The impact of HVJ-E employed in mitochondrial replacement techniques (MRTs) on embryonic development remains uncertain. This study has exhibited the influence of HVJ-E utilized in MRTs on embryonic development and has devised a novel HVJ-E-induced fusion approach to curtail the amount of HVJ-E employed in MRTs. Abstract: Mitochondrial replacement techniques (MRTs) provide a viable option for women carrying pathogenic mitochondrial DNA (mtDNA) variants to conceive disease-free offspring with a genetic connection. In comparison to electrofusion, HVJ-E-induced fusion has been identified as the most promising approach for clinical translation of MRTs due to its absence of electrical interference. However, despite confirmation of the absence of RNA activity in HVJ-E, a reduction in blastocyst quality has been observed in various MRTs studies utilizing the HVJ-E-induced fusion scheme. Recent investigations have revealed a dose-dependent elevation of reactive oxygen species (ROS) levels in various cancer cells incubated with HVJ-E. However, the impact of HVJ-E as a sole determinant on embryonic development in MRTs remains unverified. This investigation establishes that the augmented concentration of HVJ-E utilized in the conventional HVJ-E fusion protocol is an autonomous variable that influences embryonic development in MRTs. This effect may be attributed to amplified DNA damage resulting from heightened levels of ROS in reconstructed embryos. To mitigate the presence of HVJ-E in reconstructed zygotes while maintaining optimal fusion efficiency in MRTs, a novel HVJ-E-induced fusion approach was devised, namely, press-assisted fusion. This technique offers potential advantages in reducing detrimental factors that impede embryo development in MRTs.

This paper presents an automated point-of-care semen analysis method that uses smartphone imaging to visually measure sperm concentration and motility of semen samples. The proposed method follows the same visual tracking scheme as laboratory semen analysis systems, aiming to match clinical standards while being suitable for point-of-care use. A boundary-sensitive segmentation network is developed to identify and distinguish sperm from impurities in raw semen. A novel occlusion-aware multi-sperm tracking algorithm is proposed to tackle challenges posed by smartphone imaging and undiluted raw semen samples. For automated motility measurement, an occlusion-awareness module is proposed to robustly track multiple sperm during frequent sperm crossover/occlusion. The module combines the segmented contour and kinematic-based probabilistic modeling to determine the occlusion status of both targets and measurements, facilitating fundamental improvement to feasible joint event enumeration to enable robust data association. The proposed method achieved a high success rate of 95.14% for tracking occluded sperm, with low mean errors for sperm concentration (2.03 million/ml) and motility (1.58%), outperforming existing multi-sperm tracking methods. In clinical tests involving 50 participants, our method exhibited good agreement with clinical standards (Spearman rank correlation coefficients of 0.94 for concentration and 0.89 for motility) even when used by inexperienced users.

The perinuclear theca (PT) is a dense cytoplasmic web encapsulating the sperm nucleus. The physiological roles of PT in sperm biology and the clinical relevance of variants of PT proteins to male infertility are still largely unknown. We reveal that cylicin-1, a major constituent of the PT, is vital for male fertility in both mice and humans. Loss of cylicin-1 in mice leads to a high incidence of malformed sperm heads with acrosome detachment from the nucleus. Cylicin-1 interacts with itself, several other PT proteins, the inner acrosomal membrane (IAM) protein SPACA1, and the nuclear envelope (NE) protein FAM209 to form an ‘IAM–cylicins–NE’ sandwich structure, anchoring the acrosome to the nucleus. WES (whole exome sequencing) of more than 500 Chinese infertile men with sperm head deformities was performed and a CYLC1 variant was identified in 19 patients. Cylc1-mutant mice carrying this variant also exhibited sperm acrosome/head deformities and reduced fertility, indicating that this CYLC1 variant most likely affects human male reproduction. Furthermore, the outcomes of assisted reproduction were reported for patients harbouring the CYLC1 variant. Our findings demonstrate a critical role of cylicin-1 in the sperm acrosome–nucleus connection and suggest CYLC1 variants as potential risk factors for human male fertility.

IntroductionAlthough the effectiveness of pentoxifylline (PF) as a selective inhibitor of phosphodiesterase to enhance sperm motility through increasing cyclic nucleotide in cases of absolute asthenozoospermia has been demonstrated for ICSI, data related to babies born from the PF-ICSI are still severely lacking. Concerns have been raised regarding the potential embryotoxicity of PF due to the controversial results obtained from the analysis of this compound on animal embryo development. This study aimed to determine whether the application of PF to trigger frozen-thawed TESA (testicular sperm aspiration) spermatozoa increases the risk of adverse obstetric and neonatal outcomes compared with non-PF frozen-thawed TESA ICSI and conventional ICSI using fresh ejaculation.Materials and methodsA total of 5438 patients were analyzed in this study, including 240 patients underwent PF-TESA ICSI (ICSI using PF triggered frozen-thawed testicular spermatozoa), 101 patients underwent non-PF TESA ICSI (ICSI using frozen-thawed testicular spermatozoa) and 5097 patients underwent conventional ICSI using fresh ejaculation. Propensity score matching was executed to control the various characteristics of patients.ResultsNo significant differences in pregnancy outcomes were observed among the three groups (PF-TESA ICSI, non-PF TESA ICSI and conventional ICSI), including biochemical pregnancy, clinical pregnancy, implantation, miscarriage, ectopic pregnancy, multiple pregnancy, and live birth, following propensity score matching. Additionally, neonatal outcomes were found to be similar among the three groups, with no statistical differences observed in the birth defect, birth weight, gestational age, preterm birth, and early-neonatal death.Discussion and conclusionPF-ICSI may be an alternative treatment in patients using frozen-thawed testicular spermatozoa, resulting in comparable pregnancy and neonatal outcomes.

The second polar body (PB2) transfer in assisted reproductive technology is regarded as the most promising mitochondrial replacement scheme for preventing the mitochondrial disease inheritance owing to its less mitochondrial carryover and stronger operability. However, the mitochondrial carryover was still detectable in the reconstructed oocyte in conventional second polar body transfer scheme. Moreover, the delayed operating time would increase the second polar body DNA damage. In this study, we established a spindle-protrusion-retained second polar body separation technique, which allowed us to perform earlier second polar body transfer to avoid DNA damage accumulation. We could also locate the fusion site after the transfer through the spindle protrusion. Then, we further eliminated the mitochondrial carryover in the reconstructed oocytes through a physically based residue removal method. The results showed that our scheme could produce a nearly normal proportion of normal-karyotype blastocysts with further reduced mitochondrial carryover, both in mice and humans. Additionally, we also obtained mouse embryonic stem cells and healthy live-born mice with almost undetectable mitochondrial carryover. These findings indicate that our improvement in the second polar body transfer is conducive to the development and further mitochondria carryover elimination of reconstructed embryos, which provides a valuable choice for future clinical applications of mitochondrial replacement.

Mutations in mitochondrial DNA (mtDNA) contribute to a variety of serious multi-organ human diseases, which are strictly inherited from the maternal germline. However, there is currently no curative treatment. Attention has been focused on preventing the transmission of mitochondrial diseases through mitochondrial replacement (MR) therapy, but levels of mutant mtDNA can often unexpectedly undergo significant changes known as mitochondrial genetic drift. Here, we proposed a novel strategy to perform spindle-chromosomal complex transfer (SCCT) with maximal residue removal (MRR) in metaphase II (MII) oocytes, thus hopefully eliminated the transmission of mtDNA diseases. With the MRR procedure, we initially investigated the proportions of mtDNA copy numbers in isolated karyoplasts to those of individual oocytes. Spindle-chromosomal morphology and copy number variation (CNV) analysis also confirmed the safety of this method. Then, we reconstructed oocytes by MRR-SCCT, which well developed to blastocysts with minimal mtDNA residue and normal chromosomal copy numbers. Meanwhile, we optimized the manipulation order between intracytoplasmic sperm injection (ICSI) and SCC transfer and concluded that ICSI-then-transfer was conducive to avoid premature activation of reconstructed oocytes in favor of normal fertilization. Offspring of mice generated by embryos transplantation in vivo and embryonic stem cells derivation further presented evidences for competitive development competence and stable mtDNA carryover without genetic drift. Importantly, we also successfully accomplished SCCT in human MII oocytes resulting in tiny mtDNA residue and excellent embryo development through MRR manipulation. Taken together, our preclinical mouse and human models of the MRR-SCCT strategy not only demonstrated efficient residue removal but also high compatibility with normal embryo development, thus could potentially be served as a feasible clinical treatment to prevent the transmission of inherited mtDNA diseases.

Objective To explore the live birth rate and neonatal outcome after single vitrified blastocyst transfer versus single vitrified cleavage-stage embryo transfer at different grades of embryo quality. Methods A retrospective cohort study including 6077 single vitrified-thawed embryo transfer cycles was performed in the time-period from January 2013 to December 2018. Results After controlling for potential confounding variables, there are 161% increased odds of a live birth after transfer of single good quality embryo at day 5, 152% increased odds of a live birth after transfer of single poor quality embryo at day 5, 60% increased odds of a live birth after transfer of single good quality embryo at day 6 compared with transfer of single good quality embryo at day 3. Results from the generalized estimated equation regression showed significant relationship of unadjusted birth weight with development stage of embryo and embryo quality (good quality embryo on day 5 vs. Good quality embryo on day 3:β=108.55, SE=34.89, P=0.002; good quality embryo on day 6 vs. Good quality embryo on day 3:β=68.80, SE=33.75, P=0.041). However, no significant differences were seen in birth weight between transfer single poor quality embryo on day 5, 6 and transfer single good quality embryo on day 3. Conclusion A significant increase in live birth rate and birth weight after transfer of single good quality embryo on day 5 and day 6 compared with transfer of single good quality embryo on day 3 in the vitrified embryo transfer cycles.

Object: Is it possible to use different progestins cotreatment with human menopausal gonadotrophin (hMG) in women with advanced endometriosis but normal ovulation during controlled ovarian hyperstimulation (COH) in vitro fertilization (IVF)? Whether different progestins treatments can be an alternative choice for women with severe endometriosis in considering IVF/ICSI treatment remains unknown? Design: Non-inferiority randomized clinical trial. Setting: Tertiary-care academic medical center. Population: Four hundred and fifty infertile patients with severe endometriosis undergoing IVF/ICSI between May 2016 and March 2017. Methods: Four hundred and fifty infertile patients with severe endometriosis undergoing IVF/ICSI were randomized to: medroxyprogesterone acetate +hMG; dydrogesterone +hMG; and progesterone +hMG. Ovulation was induced with a gonadotropin-releasing hormone agonist (GnRH-a) and chorionic gonadotropin (hCG). Viable embryos were cryopreserved for later transfer. Main Outcome Measures: The primary endpoint outcome was the number of oocytes retrieved. Secondary indicators included the incidence of a premature surge in luteinizing hormone (LH), the number of viable embryos, and clinical pregnancy outcomes. Results: The number of oocytes retrieved was higher in the medroxyprogesterone acetate +hMG group than the two other groups (9.3 ± 5.7 vs. 8.0 ± 4.5 vs. 7.8 ± 5.2, P = 0.021). LH levels were suppressed after a 6-day progestin treatment in the medroxyprogesterone acetate +hMG and dydrogesterone +hMG groups, but there was a rebound of LH values in the progesterone +hMG group. No premature LH surge and ovarian hyperstimulation syndrome (OHSS) occurred. No significant differences among the three groups were observed in fertilization and pregnancy outcomes. Conclusion: It is mandatory to point out that our conclusions are valid for patients with ovarian advanced endometriosis but normal ovarian functions. These results suggest three different progestins protocols are equivalent in terms of pregnancy outcomes for women with advanced endometriosis. PPOS protocol can be an alternative choice for women with severe endometriosis and normal ovarian reserve in IVF/ICSI treatment. These methods could be tested with other populations of women with endometriosis. Clinical Trial Registration: www.ClinicalTrials.gov, identifier:ChiCTR-OIN-16008529. Trial registration date: 2014-05-25. Date of first patient enrollment: May 2016.

Objective: To investigate the effect of paternal body mass index (BMI) on neonatal outcomes of singletons after frozen-thawed embryo transfer (FET) cycles. Design: Retrospective cohort study. Setting: Tertiary-care academic medical center. Patient(s): A total of 7,908 singleton newborns were divided into four categories based on their paternal BMI: 284 (3.6%) infants were in the paternal underweight category, 4,678 (59.2%) infants were in the paternal normal weight category, 2,585 (32.7%) infants were in the paternal overweight category, and 361 (4.6%) infants were in the paternal obesity category. In addition, we included only infants of women with normal BMI (18.5 kg/m(2) <= BMI < 25 kg/m(2)). Intervention(s): None. Main Outcome Measure(s): Neonatal outcomes. Result(s): The rates of large for gestational age (LGA) infants were significantly higher among those in the paternal overweight and obesity categories than those in the paternal underweight categories. The rates of very LGA were higher among infants in the paternal overweight categories and lower among infants in the paternal underweight categories than the rates in normal controls. The rates of fetal macrosomia were higher among infants in the paternal overweight categories than among infants in the paternal normal weight categories. Compared with normal controls, Z-scores (gestational age- and sex-adjusted birthweight) were significantly higher among the infants in the paternal overweight and paternal obesity categories and significantly lower among the infants in the paternal underweight categories. A positive association was observed in a multiple linear regression model between paternal BMI and newborn birthweights after adjustment for several potential confounders. Conclusion(s): Paternal BMI had an independent impact on the birthweight of singletons born after FET cycles. Paternal overweight and paternal obesity were independent risk factors for having LGA infants after FET cycles. Furthermore, paternal overweight was an independent risk factor for fathering infants with macrosomia or very LGA infants after FET cycles. ((C) 2020 by American Society for Reproductive Medicine.)

Introduction Women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) protocols are typically characterised by an increased number of oocytes retrieved. The oocytes are often of poor quality, leading to lower pregnancy rates, higher miscarriage rates and an increased risk of developing ovarian hyperstimulation syndrome (OHSS). Since our previous preliminary study showed that a novel progestin-primed ovarian stimulation (PPOS) protocol blocked the luteinising hormone (LH) surge during IVF and achieved a higher pregnancy rate with a lower incidence of OHSS, we designed a prospective randomised controlled trial to compare the efficacy and safety of this PPOS protocol with the flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS who are undergoing IVF procedures. Methods and analysis Patients with PCOS will be randomised to one of two controlled ovarian stimulation regimens—GnRH antagonist or PPOS—using a computer-generated random number. A freeze-all strategy using embryo vitrification techniques and frozen embryo transfer will be performed in both groups. The primary outcome is the live-birth rate per transfer. Secondary outcomes include the incidence of premature LH surges, the duration and total dose of human menopausal gonadotropin stimulation, the number of oocytes retrieved, the incidence of moderate or severe OHSS, the number of embryos available for transfer, implantation rates, clinical pregnancy rates, pregnancy loss rates, ectopic pregnancy rates, pregnancy and neonatal complications, and congenital anomalies. The necessary sample size for this trial was estimated as 392 participants, with 196 participants in each group. Intention-to-treat analysis was used in processing our experimental data. Ethics and dissemination This study was approved by the Institutional Review Board of the hospital (2016-133-T82). The trial will be conducted according to the principles of the World Medical Association’s Declaration of Helsinki and in accordance with Good Clinical Practice standards. The findings of this trial will be published in a peer-reviewed journal. Trial registration number ChiCTRIPR16009580.

Research question: Does the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) improve the ongoing pregnancy rate of vitrified-warmed embryo transfer in women with adenomyosis undergoing IVF? Design: This retrospective study included 358 women with adenomyosis undergoing IVF. Of these, 134 women were enrolled in the LNG-IUS group and another 224 women were in the control group. All women were screened for adenomyosis by transvaginal ultrasound and magnetic resonance imaging (MRI). There was no significant difference in the ages of women, FSH, cause of infertility, body mass index, total dose of gonadotrophin used and number of oocytes collected between the two groups. All comparisons performed were between patients undergoing vitrified-warmed embryo transfer. Results: Statistical differences were found in the ongoing pregnancy rates (41.8% vs 29.5%, P = 0.017) between the LNG-IUS group and control group. Logistic regression analysis showed that the odds ratio (OR) of ongoing pregnancy was significantly increased with LNG-IUS usage (adjusted OR = 1.628, 95% confidence interval 1.011-2.622). Also, differences were found in implantation rates (32.1% vs 22.1%, P = 0.005) and clinical pregnancy rates (44% versus 33.5%, P = 0.045) between the LNG-IUS group and control group. Conclusions: The results of this study offer some support for evaluating the effect of pretreatment with LNG-IUS in women with adenomyosis in future randomized controlled trials.

Background: Endometriosis is one of the most challenging diseases for doctors helping infertile women conceive, which has become a common method to help maternal endometriosis-associated infertility. Women with advanced endometriosis possess a higher risk of several adverse outcomes both during pregnancy and at the time of delivery. Whether endometriosis gives rise to a higher occurrence of congenital abnormalities in infants via in vitro fertilization and frozen-thawed embryo transfer (IVF-ET) remains unknown. Methods: Data collected on 22,865 women undergoing IVF using a freeze-all strategy from 2007 to 2017 were analyzed to estimate the rate of congenital malformations. We used an adjusted OR to compare the fertility outcomes of women with advanced endometriosis to the control group. Results: We studied 1,495 infants born from women with advanced endometriosis and 27,105 infants born from endometriosis-free women. There was a 1.557-fold risk that the infants with advanced maternal endometriosis would develop a congenital malformation (adjusted OR: 1.557, 95% CI: 1.03-2.35). Compared with singletons, twins were 1.957 times more likely to experience an adverse outcome (OR: 1.957, 95% CI: 1.561-2.455). When analyzing specific categories of birth defects, the proportion of circulatory system defects was higher than the other categories of birth defects in total (0.56%), followed by musculoskeletal system defects (0.15%). Conclusions: Maternal advanced endometriosis might increase the risk of congenital malformations for infants born after IVF-ET. The organ system most frequently affected by congenital malformations was the cardiovascular system, followed by the musculoskeletal system.