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The objective of this study was to evaluate prevalence of chronic endometritis in a cohort of patients with retained pregnancy tissue (RPT) following miscarriage, with and without a history of recurrent pregnancy loss (RPL). In a cohort of our single academic fertility centre, we evaluated women with unexplained RPL (two or more losses) without evidence of RPT and women undergoing hysteroscopic resection of RPT following miscarriage. Endometrial samples underwent staining with H and E and CD138. A pathologist blinded to patient history recorded the number of plasma cells per 10 high power fields (HPF) and the presence or absence of endometrial stromal changes. Our main outcome measure was to measure the prevalence of chronic endometritis. Endometrial samples from 50 women with RPT following miscarriage and 50 women with unexplained RPL without evidence of RPT were reviewed. The prevalence of chronic endometritis was significantly higher in the RPT cohort (62% versus 30%). A multivariable regression demonstrated significantly higher odds of chronic endometritis in the RPT cohort, aOR 7.3 (95% CI 2.1, 25.5). We conclude that women with RPT following pregnancy loss have a high rate of chronic endometritis, suggesting that RPT is a risk factor for this disorder. Impact Statement What is already known on this subject? Known risk factors for chronic endometritis include a history of pelvic inflammatory disease, intrauterine polyps and fibroids. The aetiology for increased chronic endometritis among women with RPL is unknown. What do the results of this study add? The prevalence of chronic endometritis is significantly higher among women with retained pregnancy tissue (RPT) following miscarriage compared to women with RPL. These data presented suggest that RPT is associated with chronic endometritis among women with a history of miscarriage. What are the implications of these findings for clinical practice and/or further research? We suggest a pathologic evaluation for chronic endometritis be performed on all patients who undergo hysteroscopic resection of RPT following miscarriage. Our findings also suggest that a uterine cavity evaluation with hysteroscopy to evaluate for RPT may be reasonable in women with a history of miscarriage who are found to have chronic endometritis on endometrial biopsy. Further research is needed to determine if resection of retained tissue is sufficient to treat RPOC associated chronic endometritis, or if additional antibiotic treatment is necessary.

Purpose: To characterize the frozen oocyte disposition preferences of patients undergoing medical and planned fertility preservation., Methods: All oocyte cryopreservation (OC) patients were identified between 2015 and 2018. Demographic information and fertility preservation (FP) indication (medical or planned) were identified for each patient. Oocyte disposition options included disposal, donation to research, or donation to a specified third party, which was decided at the time of initial consent and made available in the electronic medical record. The primary outcome was the disposition selection. Secondary outcomes included differences in demographic variables and disposition selections between medical and planned FP patients using chi-squared analysis., Results: A total of 336 OC patients with a documented oocyte disposition preference were identified in the study timeframe. Patients were on average 34.5 years old (SD = 5.1) and were predominantly White (70.2%), nulliparous (83.0%), with a BMI of 24.7 (SD = 5.4). A total of 101 patients underwent OC for medical FP and 235 for planned FP. In both groups, the most commonly selected disposition option was donation to research (50% planned, 52% medical), followed by donation to a specified third party (30% planned, 30% medical), and finally disposal of oocytes (20% planned, 18% medical). There were no significant differences in disposition selection between each group. When comparing patient variables between groups, medical FP patients were more likely to be under the age of 35 and were less likely to be nulliparous (p < .001)., Conclusion: This study shows that oocyte disposition choices are similar in patients undergoing OC for medical and planned indications. As donation to research was the most commonly selected option in both groups, it is time to start thinking of streamlining ways to utilize this potential research material in the future., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To assess the relationship between maternal body mass index (BMI) and embryo morphokinetics on time-lapse microscopy (TLM)., Design: Retrospective cohort study., Methods: All IVF cycles between June 2015 and April 2017 were reviewed. Female BMI prior to egg retrieval was collected through chart review. BMI (kg/m 2 ) classification included underweight (< 18.5), normal weight (18.5-25), overweight (25-30), and obese (≥ 30). Embryos' morphokinetic parameters were assessed with TLM and included time to syngamy, 2-cell, 3-cell, 4-cell, and 8-cell. A generalized linear mixed model was used to control for potential confounders and multiple embryos resulting from a single IVF cycle., Results: A total of 2150 embryos from 589 IVF cycles were reviewed and included in the analysis. Classification based on BMI was as follows: underweight (N = 56), normal weight (N = 1252), overweight (N = 502), and obese (N = 340). After adjusting for race and use of intracytoplasmic sperm injection, the mean time to the 8-cell stage in the underweight group was 4.3 (95% CI: - 8.31, - 0.21) h less than in the normal weight group (P = 0.025) and 4.6 (95% CI: - 8.8, - 0.21) h less than in the obese group (p = 0.022). No significant difference was noted between race and TLM after controlling for possible confounders., Conclusions: Embryos from underweight women were demonstrated to have a faster time to the 8-cell stage than normal weight or obese women. No significant difference was noted for race. This study demonstrates that weight can be a factor contributing to embryo development as observed with TLM., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To develop diagnostic criteria for chronic endometritis and compare the prevalence of chronic endometritis between women with recurrent pregnancy loss (RPL) and controls., Design: Cohort study., Setting: Single academic fertility center., Patients: Women with unexplained RPL (two or more pregnancy losses) and prospectively recruited controls without a history of RPL or infertility., Interventions: Endometrial samples were stained with hematoxylin and eosin and CD138. A pathologist blinded to patient history recorded the number of plasma cells per 10 high-power fields (HPFs). In addition, the presence or absence of endometrial stromal changes was documented., Main Outcome Measure: Prevalence of chronic endometritis., Results: Endometrial samples from 50 women with unexplained RPL and 26 controls were evaluated. When chronic endometritis was defined as the presence of one or more plasma cells per 10 HPFs, 31% of controls and 56% of women with RPL met the criterion. When both endometrial stromal changes and plasma cells were required for a diagnosis of chronic endometritis, no controls and 30% of women with RPL met the criteria., Conclusions: Although rare plasma cells were found in biopsy samples from controls, the presence of both plasma cells and endometrial stromal changes was limited to the RPL cohort. We propose that chronic endometritis be defined as the presence of one or more plasma cells per 10 HPFs in the setting of endometrial stromal changes. With the use of these strict diagnostic criteria, women with RPL have a significantly higher rate of chronic endometritis, supporting an association between chronic endometritis and RPL., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Breast cancer is the most common cancer in reproductive age women, and treatment can affect fertility; however, there is often concern regarding the safety of increased estradiol (E 2 ) levels and potential delays in treatment with ovarian stimulation for fertility preservation (FP). The aim of this study was to compare recurrence and survival in breast cancer patients who pursued FP without concurrent letrozole to those who did not (non-FP)., Methods: We reviewed charts of women with breast cancer who contacted the FP patient navigator (PN) at Northwestern University from 01/2005-01/2018. Oncology and fertility outcome data were collected. Data were analyzed by Chi-square test or regression, as appropriate. Kaplan-Meier curves were used to examine breast cancer recurrence and survival. Statistical analyses were performed with SPSS IBM Statistics 26.0 for Windows., Results: 332 patients were included, of which 157 (47.3%) underwent FP. Median days to treatment after consulting the PN was 35 in the FP group and 21 in non-FP (p < 0.05). Cancer recurrence was noted in 7 (4.7%) FP patients and 13 (7.9%) non-FP patients (NS), and mortality in 5 (3.2%) FP patients and 7 (4.2%) non-FP patients (NS). Within the FP group, no significant differences were found in recurrence or mortality based on ER status, age, BMI, peak E 2 level or total gonadotropin dose. Likelihood of pursuing FP was primarily a function of age and parity, and was not affected by breast cancer stage. To date, 21 have used cryopreserved specimens, and 13 (62%) had a live birth., Conclusions: FP is safe and effective in breast cancer patients, regardless of receptor status; E 2 elevations and the 2-week delay in treatment start are unlikely to be clinically significant. These findings are unique in that our institution does not use concomitant letrozole during stimulation to minimize E 2 elevations in breast cancer patients.

Objective: To use time-lapse imaging to compare embryo morphokinetic parameters between embryos resulting in euploid pregnancy loss and euploid embryos resulting in live birth., Design: Retrospective cohort study., Setting: Single academic fertility center., Patient(s): All euploid single embryo transfers between October 2015 and January 2018., Intervention(s): Collection and analysis of baseline characteristics, cycle parameters, and outcomes., Main Outcome Measure(s): Embryo morphokinetic measurements assessed with time-lapse imaging for time to syngamy (TPNf), time to two cells, time to three cells, time to four cells, time to eight cells, time to morula, and time to blastocyst., Result(s): The study included 192 euploid single-embryo transfers. Of these, the pregnancy rate was 78% (150 of 193) and the live-birth rate was 63% (121 of 193). There were 43 transfers that did not result in pregnancy, 15 biochemical pregnancy losses, 13 clinical losses, and 121 live births. There was no statistically significant difference in age, body mass index, or number of oocytes retrieved between the groups. Unadjusted and adjusted models revealed no differences in the morphokinetics of embryos resulting in euploid miscarriage compared with those resulting in live birth., Conclusion(s): Embryos that resulted in a euploid miscarriage did not display evidence of abnormal morphokinetics on time-lapse imaging. Euploid pregnancy loss is likely multifactorial, including both embryo and endometrial factors. Further research is needed to identify factors that can predict and prevent euploid loss., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate perceptions of delayed fertility care secondary to the COVID-19 pandemic., Methods: This was a cross-sectional anonymous survey of N = 787/2,287 patients (response rate = 42.6%) from a single academic fertility center. Participants were randomized 1:1 to receive supplemental educational explaining the rationale behind recommendations to delay fertility treatments due to the COVID-19 pandemic. Assessment of well-being was conducted via the Personal Health Questionnaire Depression Scale, the Generalized Anxiety Disorder-7, the Ways of Coping-Revised, the Appraisal of Life Events Scale, and influence of supplemental education on agreement with ASRM COVID-19 Taskforce recommendations and associated distress., Results: Participants in the education v. no education groups were 35.51 (SD = 4.06) and 37.24 (SD = 5.34) years old, married (90.8% v. 89.8%), had a graduate degree (53.9% v. 55.4%), > 1 year of infertility (73.4% v. 74.4%), and were nulliparous (69.0% v. 72.6%), with moderate to high distress (64.9% v. 64.2%) (ns). Distress was related to age, duration of infertility, and engagement in social support seeking and avoidant coping strategies (P < 0.001). Agreement with recommendations was related to receipt of supplemental education, history of pregnancy loss, and use of cognitive coping (P = 0.001)., Conclusion: Most participants were distressed by the delay of treatments. Supplemental education increased acceptance of recommendations but did not decrease distress. Future treatment delays should include education related to and assessment of understanding of recommendations, and inclusion of mental health professionals in patient care.

Purpose: To compare long-term outcomes of gynecologic cancer patients who pursued controlled ovarian hyperstimulation (COH) for fertility preservation (FP) with those who did not. Methods: Retrospective cohort, COH, and health outcomes in gynecologic cancer patients; data were analyzed by chi-square test, t -tests, and logistic regression. Results: Ninety patients with a gynecologic malignancy contacted the FP patient navigator: 45.6% ( n  = 41) had ovarian cancer, 25.6% ( n  = 23) endometrial cancer, 18.9% ( n  = 17) cervical cancer, 5.6% ( n  = 5) uterine cancer, and 4.4% ( n  = 4) multiple gynecologic cancers. From this cohort, 32 underwent COH, 43 did not, and 18 pursued ovarian tissue cryopreservation (OTC; 3 patients had both COH and OTC). Median age and type of cancer were not significantly different between the groups. COH patients had a range of 1-35 oocytes retrieved. Days to next cancer treatment in the COH group was 36 days; for those who declined COH, it was 22 days (not significant [NS], p  > 0.05). There were two recurrences reported in the stimulation group and four in the no stimulation group (NS). Five deaths were reported, two in the stimulation group, none in the no stimulation group, and three in the OTC group (NS); 34% ( n  = 11) COH patients returned to use cryopreserved specimens, of which 45% ( n  = 5) had a live birth. Conclusion: Although time to next treatment was longer in the group of patients who underwent COH, this did not reach statistical significance. It appears that in selected patients with GYN malignancies, COH for oocyte or embryo cryopreservation is safe, with reasonable stimulation outcomes and no difference in long-term outcomes.

Purpose: The aim of this study is to describe the multidisciplinary approach and controlled ovarian hyperstimulation (COH) outcomes in adolescent and young adult (AYA) patients (ages 13-21) who underwent oocyte cryopreservation for fertility preservation (FP)., Methods: Multi-site retrospective cohort was performed from 2007 to 2018 at Northwestern University and Michigan University. Data were analyzed by chi-square test, t-test, and logistic regression., Results: Forty-one patients began COH of which 38 patients successfully underwent oocyte retrieval, with mature oocytes obtained and cryopreserved without any adverse outcomes. To treat this group of patients, we use a multidisciplinary approach with a patient navigator. When dividing patients by ages 13-17 vs. 18-21, the median doses of FSH used were 2325 and 2038 IU, the median number of mature oocytes retrieved were 10 and 10, and median number frozen oocytes were 11 and 13, respectively. Median days of stimulation were 10 for both groups. There was no statistical difference in BMI, AMH, peak E 2 , FSH dosage, days stimulated, total oocytes retrieved, mature oocytes retrieved, and oocytes frozen between the two groups. Three patients were canceled for poor response., Conclusion: COH with oocyte cryopreservation is a feasible FP option for AYAs who may not have other alternatives when appropriate precautions are taken, such as proper counseling and having a support team. These promising outcomes correspond to similar findings of recent small case series, providing hope for these patients to have genetically related offspring in the future.

Purpose: There is clinical evidence that early cleavage timing parameters predictive of blastocyst development also correlate with embryo implantation potential. The aim of this study is to determine the developmental competency of embryos with delayed blastulation., Methods: Retrospective study performed from 2015 to 2016 at the Division of Reproductive Endocrinology and Infertility at Northwestern University., Results: A total of 2,292 embryos from 524 patients were included. Day 6 blastocysts had statistically significant longer times for every time point analyzed than day 5 blastocysts (p < 0.001). We found no statistically significant difference in euploidy rates between day 5 (44%) and day 6 (41%) embryos (p = 0.573). t7 and t8 time points were independent predictors of euploidy after controlling for day of biopsy (p < 0.015 and p < 0.014, respectively). Intrauterine pregnancy (IUP) and live birth (LB) were less likely to occur after transferring day 6 embryos (p = 0.0033 and p = 0.0359) without previous genetic testing. However, in embryos that undergo preimplantation genetic testing for aneuploidy (PGT-A), there were no significant differences in IUP or LB rates., Conclusion: Early time-lapse points can be used to predict embryo development. Day of blastulation may be an independent predictor IUP, with day 6 blastocysts having lower pregnancy and live birth rates. Our data suggests that day 5 and day 6 PGT-A tested embryos show similar rates of euploidy, suggesting that differences in PR seen in the non-PGT-A tested group may be caused by factors other than aneuploidy. Genetic testing technologies in combination with time-lapse microscopy may provide further information to improve IVF outcomes.

Purpose: Patients undergoing in-vitro fertilization (IVF) with preimplantation genetic screening (PGS) are counseled about the limitations of this technique. As part of the consent process for PGS, physicians recommend diagnostic genetic testing performed in early pregnancy to definitively rule out chromosomal abnormalities. We have noted anecdotally, however, that few patients undergo the recommended diagnostic testing. In this study, we are examining if women who conceived using IVF-PGS did early pregnancy chromosomal testing, and if they did, what type of testing they had., Methods: This study was performed from 2015 to 2017 in the Division of Reproductive Endocrinology and Infertility at Northwestern University. We included patients who became pregnant after IVF-PGS who were seen by the Division of Reproductive Genetics and non-PGS control group., Results: Sixty-eight patients were included. A total of 50 patients (73.5%) opted for non-invasive prenatal screening; 5 (7.4%) had invasive testing (4 had chorionic villus sampling and 1 had amniocentesis). A total of 13 patients (19%) declined further genetic testing. When comparing demographic data, the mean age was significantly higher in the group of patients who pursued non-invasive testing than in the group who declined further testing (37.15 vs 34.05 years old, p < 0.05). Control group declined invasive diagnostic testing., Conclusions: Most patients who conceive using IVF-PGS do not pursue diagnostic prenatal chromosomal testing. Future studies focusing on decision making in this patient group are warranted to further elucidate why a small percentage of patients opt for diagnostic testing, even when adequately counseled about the inherent limitations of PGS.

Objective: To compare long-term outcomes of cancer patients who pursued fertility preservation (FP) with those who did not and compare random-start (RS) and menstrual cycle-specific (CS) protocols for FP., Design: Retrospective cohort., Setting: Single urban academic institution., Patient(s): Oncology patients who contacted the FP patient navigator, 2005-2015., Intervention(s): None., Main Outcome Measure(s): Time to cancer treatment, disease-free survival, and reproductive outcomes in FP versus no-FP patients and cycle outcomes for RS versus CS protocols. Data were analyzed by χ 2 and logistic regression., Result(s): Of 497 patients who met the inclusion criteria, 41% elected FP. The median number of days to cancer treatment was 33 and 19 days in the FP and no-FP groups, respectively. There was no difference in cancer recurrence or mortality. There were no differences in stimulation parameters, outcomes, or days to next cancer treatment in RS versus CS protocols. Twenty-one patients returned to use cryopreserved specimens, resulting in 16 live births. Eight of 21 returning patients used a gestational carrier. Thirteen FP (6.4%) and 16 no-FP (5.5%) patients experienced a spontaneous pregnancy., Conclusion(s): FP is both safe and efficacious for eligible cancer patients. Only 10% of patients returned to use cryopreserved specimens, and almost half used a gestational carrier, suggesting the need for further research into reproductive decision-making in cancer survivors., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe physician attitudes and variations in oncofertility treatment strategies., Methods: An exploratory online survey administered between December 1, 2014 and January 27, 2015 to 185 members of the National Physicians Cooperative (NPC)., Results: Twenty-eight percent (52 of 185) of NPC members responded to the online survey. Fifty percent of respondents were obstetrician-gynecologists working largely in academic medical centers. Thirty-eight percent stated that 14 was the youngest age they felt comfortable performing oocyte retrievals with 35% stating that any age was acceptable as long as they were postpubertal. Short stimulation protocols, utilizing a gonadotropin-releasing hormone (GnRH) antagonist (86%), were more common than long stimulation or microdose Lupron flare protocols (23% and 18%), respectively, which utilize a GnRH agonist. Random start protocols were used by 77% and over 90% perform luteal phase starts. When using random start protocols, 64% use gonadotropins only and 32% start GnRH antagonists alone for several days before starting gonadotropins. Fifty-five percent of physicians were comfortable stimulating ovarian cancer patients only after clearance from an oncologist. Aromatase inhibitors (77%) were significantly more common than tamoxifen (24%) for stimulation in breast cancer patients (p = 0.0006). When considering ovarian stimulation after chemotherapy, 24% expressed comfort only if blood counts are normal, 38% tend to wait 3 months. Regarding experimental treatment, 83% report discussing the use of GnRH agonists alone and 64% of clinics offer ovarian tissue cryopreservation., Conclusions: This study underlines the wide variation that exists in stimulation and phase start techniques, patient selection, comfort levels, and cancer type-specific decision making.

Purpose: The purpose of this study was to understand medical students' knowledge, intentions, and attitudes towards oocyte cryopreservation and employer coverage of such treatment., Methods: This cross-sectional study was performed via an online cross-sectional survey distributed to 280 female medical students from March through August 2016. Demographics, attitudes towards employer coverage, and factors influencing decision-making were assessed via a self-reported multiple-choice questionnaire. The relationship between respondents' attitudes towards employer coverage and other parameters was analyzed., Results: A total of 99 responses were obtained out of 280 female medical students. Most respondents (71%) would consider oocyte cryopreservation (potential freezers), although 8% would not consider the procedure and 21% were unsure. Seventy-six percent of respondents felt pressure to delay childbearing. Potential freezers were more likely to be single (p = 0.001), to report feeling pressure to delay childbearing (p = 0.016), and to consider egg freezing if offered by an employer (p < 0.001). Importantly, 71% percent did not view employer coverage as coercive and 77% of respondents would not delay childbearing due to employer coverage. Factors influencing decision-making in potential freezers were absence of a suitable partner (83%), likelihood of success (95%), and health of offspring (94%), among others. Knowledge about the low chance of pregnancy per oocyte (6-10%) would influence decision-making in 42% of potential freezers., Conclusion: Oocyte freezing is an acceptable strategy for the majority of young women surveyed. Pressure to delay childbearing was related to openness to freeze eggs. The majority of respondents did not find employer coverage for egg freezing coercive although further research is needed with larger, representative samples to ascertain the relationship between pressure to delay childbearing due to work demands and employer coverage for egg freezing.

Study Objective: To characterize pregnancy outcomes after hysteroscopic resection of retained products of conception (RPOCs), especially as it relates to abnormal placentation., Design: Retrospective cohort study (Canadian Task Force classification II-2)., Setting: Academic medical center., Patients: All women who underwent hysteroscopic resection of RPOCs at Northwestern Prentice Women's Hospital between January 2004 and December 2014., Interventions: Hysteroscopic resection of RPOCs., Measurements and Main Results: The medical records of all cases of hysteroscopic resection of RPOCs between January 2004 and December 2014 were reviewed. Demographic characteristics, operative findings, surgical procedure, surgical pathology, and pregnancy outcomes for preceding and subsequent pregnancies were obtained. Our primary outcome was abnormal placentation in the pregnancy after the procedure. There were a total of 55 subsequent pregnancies and 38 live births. Among these pregnancies, 54.5% (30/55) were vaginal deliveries, 34.5% (19/55) were cesarean deliveries, and 7.3% (4/55) were early pregnancy losses. Abnormal placentation was present in 18.1% of subsequent pregnancies (10/55). This consisted of 3 patients with placenta previa, 2 with placenta accreta, and 5 with retained placenta., Conclusion: Women who undergo hysteroscopic resection of RPOCs have a higher rate of abnormal placentation in subsequent pregnancies when compared with the general population. Although the etiology is likely multifactorial, the underlying pathology leading to the initial diagnosis of RPOCs is believed to play a major role., (Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.)

For patients with cancer, preserving the ability to start a family at a time of their choosing is especially important and may influence decisions pertaining to cancer treatment. For other women who have delayed childbearing for personal or professional reasons, fertility preservation offers the possibility of having a biological child regardless of age. Though these women may be interested in or benefit from fertility preservation, fertility preservation services remain underutilized. While embryo and oocyte cryopreservation remain the standard strategies for female fertility preservation recommended by the American Society of Reproductive Medicine, the American Society of Clinical Oncology and the European Society of Medical Oncology, other strategies (e.g. pharmacological protection of the ovaries and ovarian tissue cryopreservation) are the subject of increasing research. This review will present new data that have become available over the past few years pertaining to all available methods of fertility preservation.

Young women diagnosed with cancer today have a greater chance of long-term survival than ever before. Successful survivorship for this group of patients includes maintaining a high quality of life after a cancer diagnosis and treatment; however, lifesaving treatments such as chemotherapy, radiation, and surgery can impact survivors by impairing reproductive and endocrine health. Studies demonstrate that future fertility is a concern for many women diagnosed with cancer, but physician knowledge and attitudinal barriers can still prevent females from receiving care. Today, fertility preservation is an option for girls and women facing a cancer diagnosis, and emerging research is providing clinicians with an increasing number of reproductive and hormonal management tools. Physicians can play an important role in fertility by working closely with oncologists, providing patients with information about fertility preservation options prior to the start of cancer treatment, monitoring reproductive capacity after treatment, and working with cancer survivors to explore potential avenues to parenthood.