Ultrasound Evaluation of Uterine Cavity Changes After Stimulation for In Vitro Fertilization.

OBJECTIVES: Mock embryo transfer (ET) before in vitro fertilization (IVF) allows for the clinical determination of uterine cavity length (UCL) to optimize embryo placement during clinical ET. Most studies have shown that optimal pregnancy rates occur with clinical ET at a depth of 15 mm from the uterine fundus. In our study, we sought to determine the effect of ovarian stimulation and endometrial preparation on UCL using 2D transabdominal ultrasound. METHODS: We performed a retrospective cohort study comparing documented 2D transabdominal ultrasound measurements of UCL at the time of mock ET and clinical ET. Statistical analyses were performed with SPSS v. 26 with paired sample t-test and significance determined with P < .05. RESULTS: Seventy patients who underwent 91 IVF-ET cycles between 2015 and 2018 at our academic center met inclusion criteria. Patient's demographics include a median age of 34 (interquartile range [IQR]: 31, 37), gravida 1 (IQR: 0, 2), parity 0 (IQR: 0, 0), and body mass index 25.87 (IQR: 21.78, 30.01). There was a statistically significant increase in UCL by 11.9 mm after IVF stimulation (P < .001), compared to mock ET. Mean UCL at the time of mock ET was 7.66 cm (±0.98 cm) and at clinical ET was 8.85 cm (±0.98 cm). CONCLUSIONS: The uterine cavity undergoes a significant length change during ovarian stimulation and endometrial preparation. These findings confirm the remarkable uterine plasticity in response to hormonal stimulation even before pregnancy ensues. These changes in UCL should be considered during ultrasound-guided clinical ET to ensure optimal embryo placement.

Endometrial Abnormalities: Correlation Between Different Diagnostic Modalities.

OBJECTIVES: We sought to evaluate the diagnostic accuracy of transvaginal ultrasound (TVUS) saline infusion sonohysterogram (SIS), and hysteroscopy for diagnosing endometrial abnormalities and their correlation with histological findings. In addition, we sought to validate the subsistence of a more subtle abnormality called "redundant endometrium" (RE). METHODS: Retrospective cohort study of patients presenting with infertility and diagnosed with endometrial abnormalities who underwent hysteroscopy and pathology evaluation. Each patient underwent TVUS at the first visit regardless of the cycle phase, followed by SIS during proliferative phase, and then hysteroscopy, which was performed when abnormal SIS findings were diagnosed. Endometrial abnormalities were categorized as polyps (EP), RE, or normal. Frequencies of the abnormalities were recorded for the 3 imaging modalities and their sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each. RESULTS: A total of 105 TVUS and 73 SIS were performed. Because of the frequent association of EP with RE, when all endometrial pathologies were combined, the three diagnostic modalities showed high sensitivity (TVUS 88.9%, SIS 100%, hysteroscopy 82.9%, respectively), but they also showed low specificity (TVUS 56.7%, SIS 56.1%, hysteroscopy 58.2%, respectively). Pathological evaluation showed isolated RE (26 cases), to harbor polyps (19.2%), disordered endometrium (19.2%), and complex atypical hyperplasia (3.8%). CONCLUSIONS: The three diagnostic modalities showed high sensitivity in diagnosing endometrial abnormalities. We identified RE as an independent endometrial abnormality. Benign endometrium is the predominant histology in RE, however, a small proportion harbors endometrial hyperplasia. Based on these results, we advocate further evaluation when this condition is diagnosed with TVUS, or SIS.

Anti-Müllerian Hormone (AMH) regulates BRCA1 and BRCA2 gene expression after ovarian cortex transplantation.

OBJECTIVE: To test whether recombinant anti-Müllerian hormone (rAMH) could exert an inhibitory function on BRCA1/2 expression in human ovarian cortex. METHODS: Pilot study on ovariectomized nude mice xenotransplanted with human vitrified/warmed ovarian cortex and treated with rAMH via infusion pump. Twelve nude mice were ovariectomized and Alzet pumps delivering 1.23 mcg rAMH/day to reach a serum concentration of 17.5 ng/mL, or placebo (controls), were inserted intraabdominally. Previously vitrified/warmed 2x2 mm ovarian cortex fragments were transplanted on day 7 and then harvested on day 14 after pump placement. PCR analyses determined mRNA levels for BRCA1 and BRCA2 in the human ovarian cortex. RESULTS: In mice treated with rAMH, BRCA1 expression was significantly lower (0.196 fg/µg RNA, IQR 0.158, 0.236) than in controls (0.544 fg/µg RNA, IQR 0.458, 0.554; p = .030), while BRCA2 expression remained similar in rAMH mice (5.355 fg/µg RNA, IQR 4.479, 6.230) and in controls (4.011 fg/µg RNA, IQR 3.650, 4.182; p = .327). CONCLUSION: Administration of rAMH in the peri-transplant period caused downregulation of BRCA1, but not of BRCA2 expression, in human ovarian cortex. These results help our understanding of DNA repair mechanism in the ovarian cortex and identify AMH's possible protective effect on ovarian reserve in BRCA1 mutation carriers.

Pilot study establishing a nomogram of yolk sac growth during the first trimester of pregnancy.

AIM: The yolk sac (YS) has been reported as a reliable predictor of adverse pregnancy outcomes, however, it has always been evaluated cross-sectionally with a single ultrasound per patient. We sought to validate the use of YS dimensions in serial ultrasounds throughout the first 10 weeks of singleton and multiple gestations. METHODS: This was a prospective cohort study where YS diameters were serially obtained with 2D ultrasound in singleton and multiple gestations from 5 to 11 weeks. Nonparametric test were used for comparisons with P < 0.05 indicating significance. RESULTS: One hundred ninety-three patients were included, 42 twins (3 monochorionic and 39 dichorionic), 2 triplets (monochorionic twins plus a singleton) and 148 singleton pregnancies (238 total fetuses). There was no difference in YS dimensions in singleton versus multiple pregnancies. Starting at 5 weeks' gestation, the YS increased 0.4 mm (95% CI 0.3-0.5 mm) per week until 10 weeks' gestation. Forty-five fetuses were lost in the first trimester. The risk of pregnancy loss was higher with a large YS until 8 weeks (P ≤ 0.001), while after 8 weeks it was higher with a small YS (P < 0.005). CONCLUSION: We established a nomogram of YS development during the first 10 weeks of pregnancy. The YS reliably detected pregnancies that ended in loss as early as 6 weeks' gestation. The YS was either smaller or larger than in ongoing pregnancies. While all pregnancies with large YS were lost within 10 weeks, those with smaller YS were lost beyond the first 10 weeks.

Xenotransplantation of pre-pubertal ovarian cortex and prevention of follicle depletion with anti-Müllerian hormone (AMH).

OBJECTIVE: To determine whether recombinant AMH (rAMH) could prevent post-transplant follicular depletion by acting on the stemness markers Oct-4, Sox2, and NANOG. MATERIALS AND METHODS: This was an experimental study where 12 ovariectomized nude mice were xenotransplanted with vitrified/warmed ovarian cortex obtained from a pre-pubertal girl and Alzet pumps delivering rAMH, or placebo (control), were inserted intra-abdominally. Previously vitrified/warmed ovarian cortex fragments were transplanted after 7 days and then harvested after 14 days from pump placement. We performed real-time RT-PCR analyses, ELISA for AMH, FSH, and estradiol, histologic measurement of ovarian follicles, and immunohistochemistry for Ki67 and TUNEL. The main outcome measures were serum levels and tissue expression of the parameters under investigation and follicle count. RESULTS: Serum AMH, FSH, and estradiol reflected post-ovariectomy profiles and were mildly influenced by rAMH administration. Ovarian cortex expression of AMH, AMH-R2, VEGF, GDF9, Oct-4, and Sox2 was lower in rAMH mice than in controls, while NANOG was upregulated. There was a non-significant decrease in primordial follicles after vitrification-warming, and xenotransplantation further decreased this number. There were lower cell replication and depressed apoptosis in the rAMH group. CONCLUSIONS: Administration of recombinant AMH in the peri-transplant period did not protect the initial follicular depletion but decreased apoptosis and cellular activation and regulated stem cell markers' tissue expression. These results aid our understanding of the inhibitory effects of AMH on follicular development and show the benefit of administering exogenous AMH at the time of pre-pubertal ovarian cortex transplant to protect the follicles from pre-activation and premature depletion.

Clinically Relevant Female Genital Tract Anomalies.

Müllerian anomalies are defined as congenital uterine malformations that arise from improperly developing Müllerian ducts. These malformations have a variety of presentations ranging from asymptomatic to amenorrhea, dyspareunia, dysmenorrhea, chronic pelvic pain, pregnancy loss, fetal malpresentation, placental abruption, and intrauterine growth restriction. In this review, we discuss the clinical implications, diagnosis, and treatment of the various Müllerian anomalies focusing on the ones for which clinical intervention is amenable to improve pregnancy outcomes.

Relevance of Uterine Subseptations: What Length Should Warrant Hysteroscopic Resection?

OBJECTIVES: Existing recommendations warrant correction of uterine subseptations longer than 10 mm. We assessed whether a different subseptation length is indicated for intervention by evaluating the postoperative decrease in cavity width. METHODS: We conducted a prospective controlled cohort study at a university center. Healthy women and women with subseptations were evaluated with three-dimensional ultrasound before and after undergoing surgical resection of uterine subseptations by hysteroscopy. Measurement of the subseptum's length and width, and total cavity width, were obtained in both groups of women. We created a receiver operating characteristic curve using 7-mm cavity postoperative width change as the reference variable, and subseptation length as the outcome variable. Identifying a new subseptation length that warrants surgical intervention. RESULTS: Seventy-six women with subseptations and 77 with healthy uteri were included in the study. In the subseptate group, 50 had a subseptum less than 10 mm, and 26 were greater than 10 mm. Uterine and uterine cavity widths were significantly greater than in healthy women. The postoperative cavity width (28 ± 0.9 mm) was correlated with the preoperative subseptum length (R = 0.42; P = .016) and width (R = 0.54; P = .001) and was similar to healthy uteri. The receiver operator characteristic curve identified 5.9 mm (sensitivity = 100%, specificity = 41.4%) as a new threshold length of subseptation, which shows a postoperative cavity adjustment comparable to a subseptation greater than 10 mm. CONCLUSIONS: The relevance of subseptations shorter than 10 mm is currently undetermined and underestimated. Our data indicate a new subseptation cutoff length with postoperative remodeling and statistical relevance similar to longer subseptations. We propose a revision of the recommendations for surgical correction to include the objectively obtained subseptation length greater than or equal to 5.9 mm.

Fertility biomarkers to estimate metabolic risks in women with polycystic ovary syndrome.

PURPOSE: We sought to evaluate the relationship between the polycystic ovary syndrome (PCOS)-defining characteristics and the risk of developing metabolic complications in women presenting with complaints of infertility and/or menstrual irregularities and subsequently diagnosed with PCOS. METHODS: This was a cross-sectional study. Women presenting with complaints of infertility and/or irregular menses and diagnosed with PCOS by the Rotterdam criteria, underwent endocrine, metabolic, and ultrasound assessment in the early follicular phase. Reproductive and metabolic parameters were included in regression analysis models with the PCOS-defining characteristics; ROC curves were calculated for the significant predictors. RESULTS: Three hundred and seventy-four women with PCOS were included in our study. Oligo-anovulation, menstrual irregularities, and hirsutism were not predictive of any of the variables. Ovarian volume, follicle count, and biochemical hyperandrogenism were predictors for hormonal, metabolic, and endometrial complications. The relationships were independent of age and body mass index. ROC curves identified lower cut-off values of the PCOS-defining characteristics to predict patients' risks of hyperinsulinemia, dyslipidemia, and glucose intolerance. CONCLUSIONS: Adverse metabolic effects of PCOS are already present in women at the time they present complaining of infertility and/or irregular menses. Hyperandrogenism and ultrasound can assist in predicting the patients' concomitant metabolic abnormalities and can aid physicians in tailoring counseling for effective preventive strategies.

Ultrasound assessment of uterine cavity remodeling after surgical correction of subseptations.

OBJECTIVE: To assess the postoperative restoration of a normal uterine cavity, uterine cavity measurements were obtained in patients with arcuate or septate uteri in the periods before and after resection. STUDY DESIGN: Twenty-eight women diagnosed with arcuate or septate uteri were evaluated with 3-dimensional ultrasound before and after undergoing surgical resection by hysteroscopic resection, in a university center. In addition to the conventional parameters, measurements of the subseptum's length and width, and cavity width, were obtained on a frozen coronal view of the uterus. Postoperatively, uterine cavity width was measured. RESULTS: Twelve patients were diagnosed with arcuate uterus and 16 with septate uterus and subsequently underwent surgical correction. Of them, 50% had a retroverted uterus and 61% had a diagnosis of polycystic ovary syndrome (7/28, or 25%, had both). Uterine length, width, and height, before and after resection, were similar between arcuate and septate, as were the subsepti base widths, despite the different lengths. However, cavity width was significantly decreased after resection only in the septate uterus group: 3.6 cm, 95% confidence interval, 3.3-3.9, preoperatively vs 2.8 cm, 95% confidence interval, 2.5-3.1, postoperatively, respectively; P < .001. The postoperative difference in cavity width was directly correlated with the length of the subseptation (r -0.59, P = .05). CONCLUSION: Postoperative measurements of the uterine cavity revealed a remarkable uterine remodeling capacity: we speculate this could represent the most important single change to explain improved pregnancy outcomes after surgical correction of subseptations.

Coronavirus Disease 2019 (COVID-19) Vaccination and Assisted Reproduction Outcomes: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the association between coronavirus disease 2019 (COVID-19) vaccination and female assisted reproduction outcomes through a systematic review and meta-analysis. DATA SOURCES: We searched Medline (OVID), EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov on January 11, 2023, for original articles on assisted reproduction outcomes after COVID-19 vaccination. The primary outcome was rates of clinical pregnancy; secondary outcomes included number of oocytes retrieved, number of mature oocytes retrieved, fertilization rate, implantation rate, ongoing pregnancy rate, and live-birth rate. METHODS OF STUDY SELECTION: Two reviewers independently screened citations for relevance, extracted pertinent data, and rated study quality. Only peer-reviewed published studies were included. TABULATION, INTEGRATION, AND RESULTS: Our query retrieved 216 citations, of which 25 were studies with original, relevant data. Nineteen studies reported embryo transfer outcomes, with a total of 4,899 vaccinated and 13,491 unvaccinated patients. Eighteen studies reported data on ovarian stimulation outcomes, with a total of 1,878 vaccinated and 3,174 unvaccinated patients. There were no statistically significant results among our pooled data for any of the primary or secondary outcomes: clinical pregnancy rate (odds ratio [OR] 0.94, 95% CI 0.88-1.01, P =.10), number of oocytes retrieved (mean difference -0.26, 95% CI -0.68 to 0.15, P =.21), number of mature oocytes retrieved (mean difference 0.31, 95% CI -0.14 to 0.75, P =.18), fertilization rate (OR 0.99, 95% CI 0.87-1.11, P =.83), implantation rate (OR 0.92, 95% CI 0.84-1.00, P =.06), ongoing pregnancy rate (OR 0.95, 95% CI 0.86-1.06, P =.40), or live-birth rate (OR 0.95, 95% CI 0.78-1.17, P =.63). A subanalysis based on country of origin and vaccine type was also performed for the primary and secondary outcomes and did not change the study results. CONCLUSION: Vaccination against COVID-19 is not associated with different fertility outcomes in patients undergoing assisted reproductive technologies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023400023.

Inhibition of CSF1R and KIT With Pexidartinib Reduces Inflammatory Signaling and Cell Viability in Endometriosis.

Endometriosis is a common and debilitating disease, affecting ∼170 million women worldwide. Affected patients have limited therapeutic options such as hormonal suppression or surgical excision of the lesions, though therapies are often not completely curative. Targeting receptor tyrosine kinases (RTKs) could provide a nonhormonal treatment option for endometriosis. We determined that 2 RTKs, macrophage-colony stimulating factor 1 receptor (CSF1R) and mast/stem cell growth factor receptor KIT (KIT), are overexpressed in endometriotic lesions and could be novel nonhormonal therapeutic targets for endometriosis. The kinase activity of CSF1R and KIT is suppressed by pexidartinib, a small molecule inhibitor that was recently approved by the US Food and Drug Administration. Using immunohistochemistry, we detected CSF1R and KIT in endometriotic tissues obtained from peritoneal lesions, colorectal lesions, and endometriomas. Specifically, we show that KIT is localized to the epithelium of the lesions, while CSF1R is expressed in the stroma and macrophages of the endometriotic lesions. Given the high epithelial expression of CSF1R and KIT, 12Z endometriotic epithelial cells were used to evaluate the efficacy of dual CSF1R and KIT inhibition with pexidartinib. We found that pexidartinib suppressed activation in 12Z cells of JNK, STAT3, and AKT signaling pathways, which control key proinflammatory and survival networks within the cell. Using quantitative real-time polymerase chain reaction, we determined that pexidartinib suppressed interleukin 8 (IL8) and cyclin D1 (CCND1) expression. Lastly, we demonstrated that pexidartinib decreased cell growth and viability. Overall, these results indicate that pexidartinib-mediated CSF1R and KIT inhibition reduces proinflammatory signaling and cell viability in endometriosis.

Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age.

PURPOSE: AMH is used to quantify the extent of follicular pool in postpubertal women, but its value after chemotherapy is unclear. We tested AMH as a marker of follicular reserve in adult mice treated with cyclophosphamide (CTX) in prepubertal age. METHODS: Mice received placebo or CTX at age 18 days. AMH and FSH were assessed on day 43, 56, and 95 of life. Ovaries were fixed in formalin, embedded in paraffin, and stained with H&E and TUNEL. Follicular apoptosis was graded. RESULTS: All mice exposed to CTX had a decreased number of follicles/mm(2) and significantly decreased AMH, but only 48 % of pubertal and 81 % of adult mice had increased FSH. Over time, there was an increase in FSH (p < 0.05), but not a concurrent decrease in AMH, while in controls, FSH remained stable and AMH decreased. There was no correlation between histological and serological markers. CONCLUSIONS: CTX administration to pre-pubertal mice caused various degrees of residual function, which were reflected by FSH, but not by AMH or by the number of ovarian follicles. AMH served as a marker of quantitative, and FSH of qualitative, residual ovarian function.

Association between redundant endometrium and endometrial polyps: a pilot study.

BACKGROUND: The aim of this study was to explore the organic features of redundant endometrium (RE), we examined the expression of different endometrial hormone receptors, oncogenes, and cell replication markers, in normal endometrium (NE), endometrial polyps (EP) and RE specimens. METHODS: This was an experimental study examining endometrial tissue expression of estrogen receptors (ER1 and 2), progesterone receptors (PR-A+B), androgen receptor (AR), insulin receptor (Insulin-R), insulin-like growth factor receptor 1 (IGFR-1), thyroid hormone receptor (TH-RB), B-cell lymphoma 2 (Bcl-2), Ki67, HOXA10, in women with NE, EP and RE, of women undergoing hysteroscopy for benign gynecologic pathology. Specimens were separated in 3 groups: NE, EP, RE. Endometrial samples were processed for real-time RT-PCR analyses. Main outcome measure was tissue expression of the markers in the three groups. RESULTS: Of the 16 patients, 2 had NE, 8 had RE, 5 had EP, 1 had both, RE and EP. Compared to NE, RE and EP showed significantly increased Bcl-2, Insulin-R, ER-ß, PR-A+B, and TRB expression (P<0.044), with EP showing significantly increased PR-A+B, compared to RE (3.29±0.47 fg/µg RNA versus 1.86±0.34 fg/µg RNA; P=0.023). The other markers were not significantly different across the three groups: Ki67 appeared non-significantly decreased, while HOXA10, IGF-R1, AR, and ER-α, were non-significantly increased. CONCLUSIONS: RE showed biochemical characteristics different from NE. Similar to endometrial polyps, RE showed enhanced cell differentiation, but not cell replication. These changes in RE could be detrimental for embryo implantation and should be of consideration in women undergoing fertility treatments.

Take your mother's ferry: preimplantation embryo development requires maternal karyopherins for nuclear transport.

The genetic basis of preimplantation embryo arrest is slowly being unraveled. Recent discoveries point to maternally expressed proteins required for cellular functions before the embryonic genome is activated. In this issue of the JCI, Wang, Miyamoto, et al. suggest a critical role for karyopherin-mediated protein cargo transport between oocyte cytoplasm and nucleus. Defective maternal oocyte-expressed human karyopherin subunit α7 (KPNA7) and mouse KPNA2 fail to bind a critical substrate, ribosomal L1 domain-containing protein 1 (RSL1D1), affecting its transport to the nucleus. As shown in embryos of Kpna2-null females, the consequences are disrupted zygotic genome activation and arrest of development. These findings have important implications for diagnosis and treatment of female infertility.

Applicability of adult techniques for ovarian preservation to childhood cancer patients.

PURPOSE: To appraise the feasibility of current adult medical and surgical techniques for ovarian preservation in pre-pubertal and adolescent girls with cancer. METHODS: Literature search using PubMed and SCOPUS up to February 2012. In addition, the reference lists of selected studies and all identified systematic and narrative reviews were scanned for relevant references. Inclusion criteria were ovarian preservation and cancer. Exclusion criteria were non-English publications, letters, personal communications, and ovarian preservation for conditions other than cancer. RESULTS: Data from the selected publications was interpreted and discussed in the relevant sections. Cryopreservation of ovarian tissue followed by autologous transplant represents the only surgical option available for pre-pubertal girls and adolescents who cannot delay the start of chemotherapy. Few studies report on pre-pubertal and adolescent girls undergoing ovarian preservation surgeries with good harvesting, and no follow-up has been conveyed, to date. Outcomes of ovarian function after ovarian suppression with GnRH-analogs in adults have been controversial and no reports are available for pre-pubertal girls. CONCLUSIONS: Autologous transplantation of cryopreserved ovarian cortex probably represents the best option for preservation of fertility and hormonal function in childhood cancer females; however, future research needs to address the safety of this technique, especially in patients with blood-borne cancers. Ovarian suppression with GnRH-analogs at the time of chemotherapy treatment has not proven to be superior to non-suppression for fertility preservation purposes in adults. Not enough evidence is presently available in childhood cancer patients.

Options for preserving fertility in women undergoing gonadotoxic treatment.

Cancer chemotherapy and radiotherapy can be toxic to the ovaries, but women can improve their chances of preserving their fertility. Three options are available: gonadotropin-releasing hormone (GnRH) analogues, oocyte cryopreservation, and ovarian tissue cryopreservation. A fourth option, ovarian transposition, is valid for patients undergoing pelvic radiation but is not useful in patients undergoing chemotherapy.

A comparison of four systems for uterine septum diagnosis and indication for surgical correction.

INTRODUCTION: Existing guidelines do not settle on a specific length to indicate surgical incision of subseptations because of differences in the four published diagnostic methods: AFS-10 mm classification, 1988/2003, ESHRE-ESGE classification, 2013, ASRM criteria, 2016- and 5.9-mm length cut-off, 2017. With this review and data analysis we sought to identify the classification method with the most accurate association with early pregnancy loss, as to identify a subseptation length cut-off to indicate surgical correction. EVIDENCE ACQUISITION: We performed an exhaustive literature search of PubMed (MEDLINE), Embase, and Cochrane Library databases until April 20, 2020 (limited to articles published in English) of the terms "uterine septum," "arcuate uterus," "subseptation," "Müllerian anomalies," from 1980-2020. After identifying all the available classifications for uterine subseptations, we performed a secondary data analysis of our departmental database on uterine subseptations and compared the identified classification criteria. Measurement of the subseptation's length was obtained on 2-D and 3-D ultrasound in accordance with the different methods. The incidence of uterine subseptations according to each method's specifications was compared among the groups and the association with pregnancy loss was evaluated. EVIDENCE SYNTHESIS: The database comprised 125 women with uterine subseptations and all four diagnostic systems identified septate uteri within it. The 5.9-mm cut-off diagnosed 89 septate, and 36 normal uteri and was the most inclusive while the ASRM cut-off was the most restrictive one, diagnosing 92/125 as arcuate uteri, only 8/125 as septate, and 25 in the gray zone. The AFS-10 mm criteria diagnosed 92/125 as arcuate, and 33 (26.4%) as septate uteri. Subseptations were inconsistently diagnosed by the ESHRE-ESGE classification, as some subseptations longer than 10 mm would be classified as normal uteri. Five/24 women had had one previous early loss and 19/24 had recurrent pregnancy loss. The 5.9-mm system was the most sensitive, while the ASRM was the least sensitive in predicting pregnancy loss (71.2% vs. 9.5% of septate uteri). CONCLUSIONS: The proposed 5.9-mm cut-off was the most sensitive in diagnosing a septate uterus and in predicting an associated early pregnancy loss. Conversely, the AFS-10 mm and the ASRM were the most restrictive, potentially missing treatment for hazardous subseptations. This update highlights the major weaknesses in the current diagnosis of uterine subseptations and indication for surgical treatment. Standardization of clinical practice is essential for reproductive clinicians and efforts should be made to prevent even one further early pregnancy loss to uterine subseptations.

Lack of Fetal Insulin Resistance in Maternal Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) affects 8-10% of women. NIH criteria for diagnosis include chronic anovulation and evidence of clinical or biochemical hyperandrogenism. PCOS is associated with adverse neonatal outcomes. Our hypothesis is that insulin resistance is increased in fetuses born to women with PCOS. This is a prospective cohort of women who delivered at our institution. Subjects with a body mass index < 20 or ≥ 50 kg/m2, multiple gestation, and major fetal malformations were excluded. Maternal blood was collected at admission, and umbilical cord blood was collected after delivery. Serum concentrations of insulin and glucose were measured from each sample. The homeostasis model assessment index of insulin resistance (HOMA-IR) was calculated (plasma glucose (mmol/L) × insulin (µU/mL)/22.5). The HOMA-IR from mothers and fetuses with PCOS was compared with mothers and fetuses without PCOS (controls). Mann-Whitney U test was utilized for statistical analysis. Forty-six women and fetal pairs were included; 28 with PCOS and 18 controls. Maternal insulin (20 [7.7-26.5] vs. 6.6 µU/ml [5.1-7.2]; p = 0.005) and HOMA-IR (3.9 [1.6-4.5] vs. 1.1 [0.9-1.3]; p = 0.01) were increased in the PCOS group. There was no statistical difference in fetal insulin, glucose, or HOMA-IR (p = 0.31) in the umbilical artery (p = 0.10; p = 0.34; p = 0.45, respectively) or the umbilical vein (p = 0.13; p = > 0.99; p = 0.31, respectively). Insulin resistance is present in non-diabetic pregnant women with PCOS, however not in their fetuses. This might explain variations in the occurrence of the adverse neonatal and maternal outcomes reported in PCOS.

Fluid deficit calculation at hysteroscopy: could consideration of intraperitoneal fluid accumulation add insight to safety limits?

BACKGROUND: The current literature and guidelines are largely silent regarding the contribution of the fallopian tubes to the fluid deficit (FD) during hysteroscopy. We explored whether the FD could be in part due to transtubal passage. METHODS: This was a prospective cohort study. Patients who underwent hysteroscopy because of benign gynecologic pathology with, or without, laparoscopy were enrolled. The fluid deficit and, in laparoscopic cases, the amount of fluid found in the pelvis were prospectively reported. RESULTS: Comparisons between FD and intraperitoneal fluid were performed. Sixty-five patients were included in the study. Forty-five underwent hysteroscopy prior to laparoscopy and 20 patients underwent hysteroscopy-only. These were further divided into operative hysteroscopy and diagnostic hysteroscopy subgroups. In the laparoscopy group, the average FD was 525.9 mL (95% CI: 482.1-569.7) and the calculated FD due to intravasation was 286.6 mL (95%CI: 253.0-320.3). In the hysteroscopy without laparoscopy group, the average FD was 303.0 mL (95% CI: 85.2-520.8). There was no correlation between the intrauterine fluid pressure and the amount of FD, or the presence of intraperitoneal fluid. CONCLUSIONS: Most women with patent tubes undergoing hysteroscopy have accumulation of distention fluid in the pelvis and that the passage was not correlated with the intrauterine fluid pressure. These findings add new insight to the current guidelines, suggesting more accurate and patient-centered safety protocols.