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Many studies have sought to explore the impact of high-dose gonadotropin on stimulation outcomes based on a hypothesis that higher doses of follicle-stimulating hormone may harm the quantity or quality of oocytes and, therefore, be counterproductive. Herein, we describe the results of a narrative review aimed at elucidating any harm associated with "excess" follicle-stimulating hormone dosing in poor-to-moderate responders. Additionally, we sought to describe the outcomes associated with mild ovarian stimulation, with an eye toward determining whether this approach is superior. We concluded that there is no apparent harm to higher-dose gonadotropin stimulation for poor-to-moderate responders. Simultaneously, we did not find compelling data to suggest that mild stimulation is superior. Finally, we close by presenting data that suggest that more gonadotropin may be beneficial in specific clinical scenarios.

Our primary objective is to verify or refute a 2013 study by Connolly et al. which showed that in early pregnancy a gestational sac was visualized 99% of the time on transvaginal ultrasound when the HCG level reached 3,510 mIU/mL. Our secondary objective was to make clinical correlations by assessing the relationship between human chorionic gonadotropin (HCG) level in early pregnancy when a gestational sac is not seen with pregnancy outcomes of live birth, spontaneous abortion, and ectopic pregnancy. This retrospective study includes 144 pregnancies with an outcome of live birth, 87 pregnancies with an outcome of spontaneous abortion, and 59 ectopic pregnancies. Logistic regression is used to determine the probability of visualizing a gestational sac and/or yolk sac based on HCG level. A gestational sac is predicted to be visualized 50% of the time at an HCG level of 979 mIU/mL, 90% at 2,421 mIU/mL, and 99% of the time at 3,994 mIU/mL. A yolk sac was predicted to be visualized 50% of the time at an HCG level of 4,626 mIU/mL, 90% at 12,892 mIU/mL, and 99% at 39,454 mIU/mL. 90% of ectopic pregnancies presented with an HCG level below 3,994 mIU/mL. These results are in agreement with the study by Connolly et al. Since most early ectopic pregnancies had an HCG value below the discriminatory level for gestational sac visualization, other methods for evaluation of pregnancy of unknown location such as repeat HCG values are clinically important.

To determine the best-fit live birth rate per embryo based on maternal age, embryo stage, and embryo morphology.Retrospective data analysis.Fertility clinics.The patients included were treated with in vitro fertilization in the United States at clinics reporting data to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. We analyzed live birth data of unbiopsied autologous cleavage and blastocyst stage embryos for cycles started from 2016 through 2018. The analysis included 223,377 embryo transfers with a total of 336,888 embryos.None.Live birth rate per embryo and rate of multiple gestations per pregnancy.At the mean maternal age of 34 years, fresh embryos produced live birth rates of 19%, 38%, 26%, and 27% for embryos aged 3, 5, 6, and 7 days, respectively. At the age 34 years, live birth rates for day 5 fresh embryos by overall morphology grade were 43% for good, 30% for fair, and 21% for poor. For the transfer of 2 fresh day 5 blastocysts, the rate of multiple gestations per pregnancy was 47% at 25 years old, 44% at 30 years old, 35% at 35 years old, and 23% at 40 years old.The analysis of pregnancy data in the Society for Assisted Reproductive Technology database can be used to calculate live birth rates per embryo based on maternal age, embryo age, and morphology. This information can be used for evidence-based decision making, quality control, and planning multicenter studies.

The association between early surgical menopause and increased mortality has been well demonstrated. Prior studies have also demonstrated that ovarian conservation is not associated with worse oncologic outcomes in early-stage cervical cancer. This study examined the contemporary trends and characteristics of ovarian conservation at time of hysterectomy in young women with cervical cancer.This is a retrospective cohort study examining the National Inpatient Sample. The study population was 4900 women aged ≤50 years with cervical cancer who had hysterectomy-based surgical treatment from 10/2015 to 12/2018. The exposure allocation was the adnexal procedure status (ovarian conservation versus oophorectomy). The main outcome measures were temporal trends of ovarian conservation over time and per patient age. Multivariable binary logistic regression model was fitted to identify independent characteristics associated with ovarian conservation. A classification-tree was constructed by recursive partitioning analysis to examine the utilization patterns of ovarian conservation.A total of 2,940 (60.0%) women underwent ovarian conservation at hysterectomy. Ovarian conservation rates remained stable until age 37 years, ranging from 82.5% to 77.9% (P = 0.502), after which time the rate sharply and significantly decreased by 7.4% (95% confidence interval 5.4-9.3, P 0.001) in one-year age increments from 77.9% at age 37 years to 28.7% at age 50 years. The rate of ovarian conservation increased from 54.7% in Q4/2015 to 64.4% in Q4/2018 (P = 0.002). In multivariable analysis, recent surgery remained an independent factor for ovarian conservation (adjusted-odds ratio per year-quarter 1.04, 95% confidence interval 1.03-1.06). A classification-tree model identified 24 unique patterns of ovarian conservation based on patient factor (age, race/ethnicity, primary expected payer, and year of surgery), surgical factor (minimally invasive hysterectomy), and facility factor (hospital bed capacity and region), ranging from20% to 90% (absolute percentage difference,80%).Increasing rates of ovarian conservation at the time of hysterectomy in women undergoing surgical management of cervical cancer is encouraging; however, the marked decrease noted in patients in their mid-30s as well as substantial variability in ovarian conservation based on patient, surgical, and hospital factors are striking and warrant further consideration in clinical practice guidelines.

Purpose To examine patient and hospital characteristics related to seasonal fluctuation in in vitro fertilization (IVF). Methods This retrospective cohort study examined 33,077 oocyte retrievals identified in the National Ambulatory Surgery Sample. Exposure assignment was monthly IVF encounters: low-volume months (75%ile). Main outcomes were patient and hospital characteristics related to the exposure groups, assessed with a multinomial regression model. Results The median IVF encounters were 977 per month, ranging from 657 to 1074 (absolute-difference 417). January, July, and December were the lowest-quartile volume months, ranging from 657 to 710 encounters per month (low-volume months). May, August, and November were the top-quartile volume months, ranging from 1049 to 1074 encounters per month (high-volume months). In a multivariable analysis, patients undergoing IVF in the low-volume months were younger and less likely to have infertility or comorbidities. Patients undergoing IVF in the high-volume months were more likely to have lower household income and receive IVF at urban teaching facilities. Northeastern residents were less likely to have IVF in the low-volume months but more likely to have IVF in the high-volume months. Sensitivity analyses showed that the lowest-to-highest variability in monthly IVF encounters was higher in Northeast region compared to other regions (320 vs 50–128); infertility patients compared to those without (317 vs 190); privately insured patients compared to self-pay (227 vs 156); and older patients compared to younger (234 vs 192). Conclusion This study suggests substantial seasonal fluctuation in IVF oocyte retrieval in the USA based on patient and hospital factors.

Objective To investigate the efficacy of elagolix when administered at different time points in a menstrual cycle. Design Clinical case series. Setting Academic reproductive endocrinology center. Patients Ovulatory women not desiring pregnancy. Intervention(s) Six doses of elagolix 200 mg were administered over 4 days, starting at 3 different points in a menstrual cycle: early follicular; late follicular; and midluteal. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P) concentrations were measured at baseline, during elagolix administration, and 1 day after the last dose. Transvaginal ultrasounds were performed to monitor follicle sizes. Main Outcome Measure(s) Serum FSH, LH, E2, and P. Result(s) Twelve women, four per group, completed the study. Subjects were 23–42 years of age. Demographics and ovarian reserve parameters were similar among participants. Elagolix suppressed FSH, LH, E2, and P when administered in the early follicular and midluteal phases but had mixed results when administered in the late follicular phase. Two participants demonstrated suppression of all four hormones. One participant ovulated, indicated by an increase in P concentration and development of a corpus luteum. A second participant did not ovulate yet demonstrated an increase in E2 concentration with growth of a dominant follicle. There were no significant differences in median percent change of hormone concentrations across study groups. Conclusion(s) The results of this study suggest that elagolix can suppress the hypothalamic–pituitary–ovarian axis when initiated at different points in a menstrual cycle. Optimal dosing and treatment window for consistent hormone suppression have yet to be determined. Clinical Registration Number NCT04060992

The purpose of this study is to determine if trophectoderm biopsy prior to autologous frozen blastocyst transfer in programmed cycles is associated with gestational age at delivery, birth weight, or cesarean rate in viable singleton gestations. We conducted a retrospective cohort study of patients at a university-affiliated center that had viable singleton gestations after autologous frozen blastocyst transfer in programmed cycles. Obstetrical outcomes of 67 pregnancies after blastocyst trophectoderm biopsy for preimplantation genetic testing were compared to 78 pregnancies from unbiopsied blastocysts. There were no significant differences between the two cohorts in terms of maternal age, BMI, or ethnicity. There were no differences in the preimplantation genetic testing cohort compared to the reference cohort for median gestational age at delivery (39.4 vs 39.4 weeks, p = 0.80), median birth weight (3420 vs 3430 g, p = 0.97), cesarean rate (51% vs 44%, p = 0.41), preterm delivery rate (12% vs 8%, p = 0.41), rate of low birth weight (12% vs 9%, p = 0.59), or rate of birth weight over 4000 g (13% vs 8%, p = 0.29). There were no differences in the primary outcomes with subgroup analysis based on fetal sex, single embryo transfer, gravidity, history of prior term birth, and maternal age < or ≥ 35 years. Trophectoderm biopsy prior to frozen blastocyst transfer in programmed cycles was not associated with adverse obstetrical outcomes related to gestational age at delivery, birth weight, or cesarean rate.

IntroductionPrevious studies have suggested that metformin use may enhance the therapeutic effect of progestin therapy for endometrial hyperplasia or malignancy. However, it is not known how the impact of concurrent metformin may be altered by route of progestin therapy, either locally via an intrauterine device or systemically. This study examined the effectiveness of concurrent metformin use and progestin therapy for women with complex atypical hyperplasia stratified by progestin route (systemic vs local).MethodsThis single-institution retrospective study examined consecutive women with complex atypical hyperplasia who received progestin therapy from 2003 to 2018. Time-dependent analyses for complete response rate were performed comparing concurrent metformin users versus non-users in the oral progestin group and in the levonorgestrel-releasing intrauterine device group.ResultsAcross the study cohort (n=245), there were 137 (55.9%) women who responded to progestin therapy. In the oral progestin group (n=176), the median age and body mass index were 36 years and 37.7 kg/m2, respectively. 36 (20.5%) of women on oral progestins also took metformin. After controlling for diabetes status, women taking both oral progestins and metformin had a complete response rate similar to those not taking metformin (6 month cumulative rates, 23.1% vs 27.8%, adjusted hazard ratio (aHR) 0.71, 95% confidence interval (95% CI) 0.36 to 1.41). In the levonorgestrel-releasing intrauterine device group (n=69), the median age and body mass index were 35 years and 39.9 kg/m2, respectively. There were 15 (21.7%) women who took metformin in addition to the levonorgestrel-releasing intrauterine device. After controlling for diabetes status, women who had the levonorgestrel-releasing intrauterine device and took metformin had a significantly higher complete response rate compared with those not taking metformin (6 month cumulative rates, 86.7% vs 58.9%, aHR 2.31, 95% CI 1.09 to 4.89).ConclusionIn a predominantly obese population, concurrent metformin may possibly offer treatment benefit when used with the levonorgestrel-releasing intrauterine device.

OBJECTIVE To analyse populational trends and perioperative complications following conservative surgery versus oophorectomy in women

The utilization of preimplantation genetic testing for aneuploidy (PGT-A) has understandable intuitive appeal in reassuring the clinician that ‘everything possible’ has been done to assure the birth of a healthy baby. Whereas the development of the PGT-A technology is still in a relatively early stage, great strides have nevertheless been made in the understanding of the genetics of the preimplantation human embryo. The problem lies not in the progress that has been achieved, but rather, in the reality that PGT-A is being actively marketed as a mature technology. Those that market the technology overstate its benefits and underestimate the losses of potential implantations that are the consequence of the practice of PGT-A. The implication is that the PGT-A technology is accurate, has minimal errors and is ready to be applied to every case of IVF. This approach is not evidence-based. Substantial losses of potential implantations are even evident in the analysis of the numbers presented by marketing materials themselves. In order to provide accurate, evidence-based counseling for patients undergoing IVF, we need to apply an appropriate level of scientific scrutiny to the data that are available and apply PGT-A selectively to those cases in which the benefits clearly outweigh the costs.

Purpose To compare ovulation rates between Letrozole and Clomiphene Citrate (CC) using a stair-step protocol to achieve ovulation induction in women with Polycystic Ovarian Syndrome (PCOS). Methods This is a retrospective cohort of predominantly Hispanic PCOS women of reproductive age who completed ovulation induction (OI) comparing women who underwent Letrozole stair-step protocol to those who underwent OI with CC stair-step. All women had a diagnosis of PCOS based on the 2003 Rotterdam criteria. For both protocols, sequentially higher doses of Letrozole or CC were given 7 days after the last dose if no dominant follicles were seen on ultrasonography. The primary outcome was ovulation rate (determined by presence of a dominant follicle) between the two treatment groups. Secondary outcomes included time to ovulation, clinical pregnancy rates and side effects. Results 49 PCOS patients completed a Letrozole stair-step cycle and 43 completed a CC stair-step cycle for OI. Overall, demographics were comparable between both groups. Ovulation rates with the Letrozole stair-step protocol were equivalent to CC stair-step protocol (96% vs 88%, p = 0.17). Although the mean time (days) to ovulation was shorter in the Letrozole group (19.5 vs 23.1, p = 0.027), the pregnancy rates were similar for both groups. Conclusions This is the first study to date that has compared the efficacy of the stair-step protocol in PCOS patients using Letrozole and CC. Both Letrozole and CC can be prescribed in a stair-step fashion. Letrozole stair-step was as efficacious as CC stair-step; patients achieved comparable rates of ovulation and clinical pregnancy. Time to ovulation was shorter in the Letrozole protocol.

OBJECTIVE: To profile patient characteristics associated with and outcomes of ovarian conservation at the time of hysterectomy in young women with minimal-risk endometrial cancer. METHODS: A population-based retrospective analysis of the Nationwide Inpatient Sample between 2007 and 2015 was performed. Women aged 2 days (relative risk reduction, 16.7%, P < 0.001). Rates of surgical complications were not different between the two groups (8.2% versus 8.3%, P = 0.91). In the benign gynecologic disease and cervical cancer cohorts, ovarian conservation was also associated with decreased length of hospitalization (all, P < 0.05). CONCLUSION: There is substantial variability in the utilization of ovarian conservation in young women with minimal-risk endometrial cancer based on patient, surgical, and hospital factors. Our study suggests that guidelines for ovarian conservation in this population would be helpful for improving patient selection and rates of ovarian conservation.

Imatinib is an oral chemotherapeutic used primarily to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). The potential effects of cancer treatments on a patient’s future fertility are a major concern affecting the quality of life for cancer survivors. The effects of imatinib on future fertility are unknown. It is teratogenic. Therefore, patients are advised to stop treatment before pregnancy. Unfortunately, CML and GIST have high rates of recurrence in the absence of the drug, therefore halting imatinib during pregnancy endangers the mother. Possible long-term (post-treatment) effects of imatinib on reproduction have not been studied. We have used a mouse model to examine the effects of imatinib on the placenta and implantation after long-term imatinib exposure. We found significant changes in epigenetic markers of key imprinted genes in the placenta. There was a significant decrease in the labyrinth zone and vasculature of the placenta, which could impact fetal growth later in pregnancy. These effects on placental growth occurred even when imatinib was stopped prior to pregnancy. These results indicate potential long-term effects of imatinib on pregnancy and implantation. A prolonged wash-out period prior to pregnancy or extra monitoring for possible placental insufficiency may be advisable.

PURPOSE: To determine if oocyte denudation and ICSI at 36.5 versus 39 h post HCG and/or Lupron trigger (2.5 h versus 5 h post-oocyte retrieval) influences fertilization and blastulation rates in good prognosis couples METHODS: We performed a prospective, randomized controlled trial of 12 patients undergoing IVF with ICSI at an academic fertility center, resulting in 206 MII oocytes analyzed. At time of retrieval, patients with more than 10 oocytes retrieved had their oocytes randomized into two groups—one group for oocyte denudation and ICSI at 36.5 h post HCG and/or Lupron trigger and the other group for these procedures at 39 h post HCG and/or Lupron trigger (2.5 and 5 h after oocyte retrieval). Primary outcomes were fertilization and blastulation rates. RESULTS: No difference was observed in fertilization rate, total blastulation rate, or day of blastulation based on timing of denudation and ICSI (all p > 0.05). Multiple regression analyses for fertilization and blastulation controlling for age and BMI revealed no difference in fertilization based on time of ICSI (p = 0.38, 0.71, respectively). A conditional logistic regression to account for multiple oocytes derived from each patient also found no difference in fertilization or blastulation based on timing of ICSI, even when controlling for age and BMI (p = 0.47, 0.59, respectively). CONCLUSION(S): In good prognosis couples, we observed no difference in fertilization or blastulation rates based on timing of ICSI within the currently accepted 2- to 6-h window post-retrieval based on a 34-h trigger. The oocyte appears to have a physiological tolerance for fertilization during this window of time, and variability in the timing of ICSI during this window is unlikely to have an impact on cycle outcome.

Research question What impact does maternal age and embryo morphology have on sustained implantation rates of euploid blastocysts? Design This was a retrospective analysis of sustained implantation rates of euploid blastocysts stratified by maternal age and morphology. The primary analysis included 208 embryo transfers with a total of 229 embryos transferred from January 2017 through August 2020. Results For all ages the sustained implantation rates for day 5 good quality blastocysts were higher than for day 5 fair, day 5 poor and day 6 blastocysts. At a maternal age of 36 years the best-fit sustained implantation rates were 86% for day 5 good quality blastocysts, 64% for day 5 fair, 63% for day 5 poor, and 51% for all day 6 blastocysts analysed as one group. When controlling for morphology and day of biopsy, there were higher sustained implantation rates for euploid embryos of younger patients compared with older patients. The best-fit sustained implantation rates for age 33 compared to age 39 years were 86% versus 80% for day 5 good, 71% versus 62% for day 5 fair, 59% versus 55% for day 5 poor, and 81% versus 46% for all day 6. Conclusions There was a clinically significant higher sustained implantation rate at all ages for euploid day 5 good quality embryos compared with day 5 fair, day 5 poor and day 6 embryos.

The purpose of this study is to determine if trophectoderm biopsy prior to autologous frozen blastocyst transfer in programmed cycles is associated with gestational age at delivery, birth weight, or cesarean rate in viable singleton gestations. We conducted a retrospective cohort study of patients at a university-affiliated center that had viable singleton gestations after autologous frozen blastocyst transfer in programmed cycles. Obstetrical outcomes of 67 pregnancies after blastocyst trophectoderm biopsy for preimplantation genetic testing were compared to 78 pregnancies from unbiopsied blastocysts. There were no significant differences between the two cohorts in terms of maternal age, BMI, or ethnicity. There were no differences in the preimplantation genetic testing cohort compared to the reference cohort for median gestational age at delivery (39.4 vs 39.4 weeks, p = 0.80), median birth weight (3420 vs 3430 g, p = 0.97), cesarean rate (51% vs 44%, p = 0.41), preterm delivery rate (12% vs 8%, p = 0.41), rate of low birth weight (12% vs 9%, p = 0.59), or rate of birth weight over 4000 g (13% vs 8%, p = 0.29). There were no differences in the primary outcomes with subgroup analysis based on fetal sex, single embryo transfer, gravidity, history of prior term birth, and maternal ageor ≥ 35 years. Trophectoderm biopsy prior to frozen blastocyst transfer in programmed cycles was not associated with adverse obstetrical outcomes related to gestational age at delivery, birth weight, or cesarean rate.

To study the impact of body habitus on risk of complications resulting from ovarian hyperstimulation syndrome (OHSS) in hospitalized patients. This is a retrospective observational study examining the National Inpatient Sample between January 2012 and September 2015. Patients were women

The formation of differential cell lineages in the mammalian blastocyst from the totipotent zygote is crucial for implantation and the success of the whole pregnancy. The first lineage segregation generates the polarised trophectoderm (TE) tissue, which forms the placenta, and the apolar inner cell mass (ICM), which mainly gives rise to all foetal tissues and also the yolk sac1–3. The mechanism underlying this cell fate segregation has been extensively studied in the mouse embryo4,5. However, when and how it takes place in the human embryo remains unclear. Here, using time-lapse imaging and 325 surplus human embryos, we provide a detailed characterisation of morphological events and transcription factor expression and localisation to understand how they lead to the first lineage segregation in human embryogenesis. We show that the first lineage segregation of the human embryo is triggered by cell polarisation that occurs at the 8-cell stage in two sequential steps. In the first step, F-actin becomes apically polarised concomitantly with embryo compaction. In the second step, the Par complex becomes polarised to form the apical cellular domain. Mechanistically, we show that activation of Phospholipase C (PLC) triggers actin polarisation and is therefore essential for apical domain formation, as is the case in mouse embryos6. Finally, we show that, in contrast to the mouse embryo, the key extra-embryonic determinant GATA37,8 is expressed not only in extra-embryonic lineage precursors upon blastocyst formation. However, the cell polarity machinery enhances the expression and nuclear accumulation of GATA3. In summary, our results demonstrate for the first time that cell polarisation reinforces the first lineage segregation in the human embryo.

Objective: To describe the current practice indications, methodology, and outcomes from a real-world experience of intravaginal culture (IVC) using INVOCELL. Design: A descriptive study outlining real-world experience with INVOCELL that addresses patient selection, ovarian stimulation, embryology laboratory practices, and outcomes. Setting: Five fertility centers in Missouri, Texas, North Carolina, South Carolina, and Virginia. Patients: Four hundred sixty-three patients undergoing 526 cycles. Intervention: IVC using INVOCELL. Main Outcome Measures: Cumulative pregnancy rate and live births. Secondary outcomes of interest included percent good quality embryos. Results: IVC with INVOCELL was primarily used in women 0.8 ng/mL. The mean numbers of retrieved oocytes ranged from 9.2 to 16. Mean numbers of oocytes and sperm-injected oocytes loaded per INVOCELL ranged from a mean of 6.4–9.5 with a reported maximum of 34 oocytes loaded into the device. Most (95%) of the embryos were transferred on day 5. The mean blastocyst recovery per oocyte loaded into the device ranged from 19% to 34%; mean cumulative live birth plus ongoing pregnancy rates ranged from 29% to 53% per cycle start and 40% to 61% per transfer. Conclusions: This study of IVC using INVOCELL as an alternative model for infertility treatment confirms its utility as a viable alternative to standard incubator-based in vitro fertilization. The technology is compatible within the current framework of practice patterns and, when appropriately used, results in acceptable blastocyst recovery and live birth rates. Further use of INVOCELL in other clinical situations is warranted.

Aim Epithelial ovarian cancer (EOC) can be a devastating diagnosis in women of reproductive age who desire future fertility. However, in early-stage disease, fertility-sparing surgery (FSS) can be considered in appropriately selected patients. Methods This is a narrative descriptive review of the recent literature on FSS for EOC from oncologic, reproductive and endocrinologic perspectives. Results The recurrence rate following FSS performed for stage I EOC in published retrospective studies collectively is 13% but ranges from 5 to 29%, while mortality ranges from 0 to 18%. Five-year disease-free survival following FSS is over 90% but decreases with higher stage and grade. Recurrences following FSS are more likely to be localized with a more favorable prognosis compared to recurrences following radical surgery. Adjuvant chemotherapy is recommended in women with high-risk disease, and strategies to minimize gonadotoxicity during chemotherapy such as gonadotropin-releasing hormone (GnRH) agonists may be considered. Oocyte, embryo and/or ovarian cryopreservation can also be offered to patients desiring future biologic children. Reproductive outcomes following FSS, including pregnancy and miscarriage rates, resemble those of the general population, with a chance of successful pregnancy of nearly 80%. Conclusion In retrospective data, FSS appears to be oncologically safe in stage IA and IC grade 1-2 non-clear cell EOC. In patients with grade 3 tumors or clear cell histology, treatment can be individualized, weighing a slightly higher risk of recurrence with fertility goals. A multidisciplinary approach with oncology and reproductive endocrinology may be of utility to help these patients achieve their fertility goals.

BACKGROUND: Though hysterectomy remains the standard treatment for complex atypical hyperplasia, patients who desire fertility or who are poor surgical candidates may opt for progestin therapy. However, the effectiveness of the levonorgestrel-releasing intrauterine device compared to systemic therapy in the treatment of complex atypical hyperplasia has not been well studied. OBJECTIVE: We sought to examine differences in treatment response between local progestin therapy with the levonorgestrel-releasing intrauterine device and systemic progestin therapy in women with complex atypical hyperplasia. METHODS: This single-institution retrospective study examined women with complex atypical hyperplasia who received progestin therapy between 2003 and 2018. Treatment response was assessed by histopathology on subsequent biopsies. Time-dependent analyses of complete response and progression to cancer were performed comparing the levonorgestrel-releasing intrauterine device and systemic therapy. A propensity score inverse probability of treatment weighting model was used to create a weighted cohort that differed based on treatment type but was similar with respect to other characteristics. An interaction-term analysis was performed to examine the impact of body habitus on treatment response, and an interrupted time-series analysis was employed to assess if changes in treatment patterns correlated with outcomes over time. RESULTS: A total of 245 women with complex atypical hyperplasia received progestin therapy (levonorgestrel-releasing intrauterine device n = 69 and systemic therapy n = 176). The mean age and body mass index were 36.9 years and 40.0 kg/m(2), respectively. In the patient-level analysis, women who received the levonorgestrel-releasing intrauterine device had higher rates of complete response (78.7% vs 46.7%; adjusted hazard ratio, 3.32; 95% confidence interval, 2.39–4.62) and a lower likelihood of progression to cancer (4.5% vs 15.7%; adjusted hazard ratio, 0.28; 95% confidence interval, 0.11–0.73) compared to those who received systemic therapy. In particular, women with class III obesity derived a higher relative benefit from levonorgestrel-releasing intrauterine device therapy in achieving complete response compared to systemic therapy: class III obesity, adjusted hazard ratio 4.72, 95% confidence interval 2.83–7.89; class I–II obesity, adjusted hazard ratio 1.83, 95% confidence interval 1.09–3.09; and nonobese, adjusted hazard ratio 1.26, 95% confidence interval 0.40–3.95. In the cohort-level analysis, the obesity rate increased during the study period (77.8% to 88.2%, 13.4% relative increase, P =.033) and levonorgestrel-releasing intrauterine device use significantly increased after 2007 (6.3% to 82.7%, 13.2-fold increase, P < .001), both concomitant with a higher proportion of women achieving complete response (32.9% to 81.4%, 2.5-fold increase, P = .005). CONCLUSION: Our study suggests that local therapy with the levonorgestrel-releasing intrauterine device may be more effective than systemic therapy for women with complex atypical hyperplasia who opt for nonsurgical treatment, particularly in morbidly obese women. Shifts in treatment paradigm during the study period toward increased levonorgestrel-releasing intrauterine device use also led to improved complete response rates despite increasing rates of obesity.