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Infertility: HELP
Articles by Richard S. Legro
Based on 69 articles published since 2008
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Between 2008 and 2019, Richard S. Legro wrote the following 69 articles about Infertility.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME - PART 2. 2015

Goodman, Neil F / Cobin, Rhoda H / Futterweit, Walter / Glueck, Jennifer S / Legro, Richard S / Carmina, Enrico / Anonymous3000851 / Anonymous3010851 / Anonymous3020851. · ·Endocr Pract · Pubmed #26642102.

ABSTRACT: Polycystic ovary syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists and the Androgen Excess Society aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2014. Insulin resistance is believed to play an intrinsic role in the pathogenesis of PCOS. The mechanism by which insulin resistance or insulin give rise to oligomenorrhea and hyperandrogenemia, however, is unclear. Hyperinsulinemic-euglycemic clamp studies have shown that both obese and lean women with PCOS have some degree of insulin resistance. Insulin resistance is implicated in the ovulatory dysfunction of PCOS by disrupting the hypothalamic-pituitary-ovarian axis. Given the association with insulin resistance, all women with PCOS require evaluation for the risk of metabolic syndrome (MetS) and its components, including type 2 diabetes, hypertension, hyperlipidemia, and the possible risk of clinical events, including acute myocardial infarction and stroke. Obese women with PCOS are at increased risk for MetS with impaired glucose tolerance (IGT; 31 to 35%) and type 2 diabetes mellitus (T2DM; 7.5 to 10%). Rates of progression from normal glucose tolerance to IGT, and in turn to T2DM, may be as high as 5 to 15% within 3 years. Data suggest the need for baseline oral glucose tolerance test every 1 to 2 years based on family history of T2DM as well as body mass index (BMI) and yearly in women with IGT. Compared with BMI- and age-matched controls, young, lean PCOS women have lower high-density lipoprotein (HDL) size, higher very-low-density lipoprotein particle number, higher low-density lipoprotein (LDL) particle number, and borderline lower LDL size. Statins have been shown to lower testosterone levels either alone or in combination with oral contraceptives (OCPs) but have not shown improvement in menses, spontaneous ovulation, hirsutism, or acne. Statins reduce total and LDL cholesterol but have no effect on HDL, C-reactive protein, fasting insulin, or homeostasis model assessment of insulin resistance in PCOS women, in contrast to the general population. There have been no long-term studies of statins on clinical cardiac outcomes in women with PCOS. Coronary calcification is more prevalent and more severe in PCOS than in controls. In women under 60 years of age undergoing coronary angiography, the presence of polycystic ovaries on sonography has been associated with more arterial segments with >50% stenosis, but the relationship between PCOS and actual cardiovascular events remains unclear. Therapies for PCOS are varied in their effects and targets and include both nonpharmacologic as well as pharmacologic approaches. Weight loss is the primary therapy in PCOS--reduction in weight of as little as 5% can restore regular menses and improve response to ovulation- inducing and fertility medications. Metformin in premenopausal PCOS women has been associated with a reduction in features of MetS. Clamp studies using ethinyl estradiol/drosperinone combination failed to reveal evidence of an increase in either peripheral or hepatic insulin resistance. Subjects with PCOS have a 1.5-times higher baseline risk of venous thromboembolic disease and a 3.7-fold greater effect with OCP use compared with non-PCOS subjects. There is currently no genetic test to screen for or diagnose PCOS, and there is no test to assist in the choice of treatment strategies. Persistent bleeding should always be investigated for pregnancy and/or uterine pathology--including transvaginal ultrasound exam and endometrial biopsy--in women with PCOS. PCOS women can have difficulty conceiving. Those who become pregnant are at risk for gestational diabetes (which should be evaluated and managed appropriately) and the microvascular complications of diabetes. Assessment of a woman with PCOS for infertility involves evaluating for preconceptional issues that may affect response to therapy or lead to adverse pregnancy outcomes and evaluating the couple for other common infertility issues that may affect the choice of therapy, such as a semen analysis. Women with PCOS have multiple factors that may lead to an elevated risk of pregnancy, including a high prevalence of IGT--a clear risk factor for gestational diabetes--and MetS with hypertension, which increases the risk for pre-eclampsia and placental abruption. Women should be screened and treated for hypertension and diabetes prior to attempting conception. Women should be counseled about weight loss prior to attempting conception, although there are limited clinical trial data demonstrating a benefit to this recommendation. Treatment for women with PCOS and anovulatory infertility should begin with an oral agent such as clomiphene citrate or letrozole, an aromatase inhibitor.

2 Editorial Quo vadis randomized controlled trials in infertility? 2012

Legro, Richard S. · ·Fertil Steril · Pubmed #23084270.

ABSTRACT: -- No abstract --

3 Editorial Metformin as adjuvant therapy to IVF in women with PCOS: when is intention-to-treat unintentional? 2011

Legro, Richard S. · ·Hum Reprod · Pubmed #21606132.

ABSTRACT: -- No abstract --

4 Editorial Individualizing infertility therapy with pharmacogenomics: vanity or vanguard? 2008

Legro, Richard S. · ·Pharmacogenomics · Pubmed #18781843.

ABSTRACT: -- No abstract --

5 Review Effects of obesity treatment on female reproduction: results do not match expectations. 2017

Legro, Richard S. ·Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Electronic address: RSL1@psu.edu. ·Fertil Steril · Pubmed #28366412.

ABSTRACT: The adverse effects of obesity of female reproduction have been extensively documented. However, there are few prospective studies that have examined preconception weight loss interventions. There is a need to develop successful interventions with significant weight loss and compliance and most importantly document the effects of preconception interventions on important perinatal outcomes such as live birth and the health of the infant and mother. The existing data from randomized trials that come closest to meeting these criteria have failed to document improved live-birth rates after the intervention compared with control groups. There is a tendency to equate favorable weight change both before and during pregnancy with a direct qualitative improvement in all perinatal outcomes, yet the results from the most successful treatment of morbid obesity, that is, bariatric surgery, with on average 40% weight loss, suggest a mixed risk-benefit ratio on perinatal outcomes. Although interventions to control gestational weight gain have been more completely studied than preconception ones, and have documented successful interventions to achieve appropriate weight gain, there is no clear evidence that controlling gestational weight gain actually improves any important perinatal outcome. Future studies must develop more successful and effective interventions, capture perinatal outcomes instead of weight change as the primary outcomes, use, at least preconception, new antiobesity drugs (in combination with other therapies), and study bariatric surgery in prospective trials to improve our understanding of the effectiveness of obesity treatment before pregnancy.

6 Review Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis. 2017

Wang, Rui / Kim, Bobae V / van Wely, Madelon / Johnson, Neil P / Costello, Michael F / Zhang, Hanwang / Ng, Ernest Hung Yu / Legro, Richard S / Bhattacharya, Siladitya / Norman, Robert J / Mol, Ben Willem J. ·Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, North Adelaide, Australia r.wang@adelaide.edu.au. · Reproductive Medicine Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Robinson Research Institute, Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, North Adelaide, Australia. · Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands. · Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand. · School of Women's and Children's Health, University of New South Wales, Sydney, Australia. · Department of Obstetrics and Gynaecology, University of Hong Kong, Hong Kong, China. · Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, USA. · Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK. · FertilitySA, Adelaide, Australia. · NHMRC (National Health and Medical Research Council) Centre for Research Excellence in Polycystic Ovary Syndrome, Adelaide, Australia. · South Australian Health and Medical Research Institute, Adelaide, Australia. ·BMJ · Pubmed #28143834.

ABSTRACT: OBJECTIVE:  To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive. DESIGN:  Systematic review and network meta-analysis. DATA SOURCES:  Cochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016. STUDY SELECTION:  Randomised controlled trials comparing eight ovulation induction treatments in women with WHO group II anovulation: clomiphene, letrozole, metformin, clomiphene and metformin combined, tamoxifen, gonadotropins, laparoscopic ovarian drilling, and placebo or no treatment. Study quality was measured on the basis of the methodology and categories described in the Cochrane Collaboration Handbook. Pregnancy, defined preferably as clinical pregnancy, was the primary outcome; live birth, ovulation, miscarriage, and multiple pregnancy were secondary outcomes. RESULTS:  Of 2631 titles and abstracts initially identified, 57 trials reporting on 8082 women were included. All pharmacological treatments were superior to placebo or no intervention in terms of pregnancy and ovulation. Compared with clomiphene alone, both letrozole and the combination of clomiphene and metformin showed higher pregnancy rates (odds ratio 1.58, 95% confidence interval 1.25 to 2.00; 1.81, 1.35 to 2.42; respectively) and ovulation rates (1.99, 1.38 to 2.87; 1.55, 1.02 to 2.36; respectively). Letrozole led to higher live birth rates when compared with clomiphene alone (1.67, 1.11 to 2.49). Both letrozole and metformin led to lower multiple pregnancy rates compared with clomiphene alone (0.46, 0.23 to 0.92; 0.22, 0.05 to 0.92; respectively). CONCLUSIONS:  In women with WHO group II anovulation, letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of ovulation and pregnancy. Compared with clomiphene alone, letrozole is the only treatment showing a significantly higher rate of live birth. SYSTEMATIC REVIEW REGISTRATION:  PROSPERO CRD42015027579.

7 Review Ovulation induction in polycystic ovary syndrome: Current options. 2016

Legro, Richard S. ·Department of Obstetrics and Gynecology and Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. Electronic address: RSL1@PSU.EDU. ·Best Pract Res Clin Obstet Gynaecol · Pubmed #27866938.

ABSTRACT: There are a variety of effective treatment options to induce ovulation in women with polycystic ovary syndrome (PCOS). The most effective treatments are primarily reproductive and target the hypothalamic-pituitary-ovarian (HPO) axis. Letrozole, an aromatase inhibitor, is headed toward replacing clomiphene, a selective estrogen receptor modulator, as the first-choice option. Metabolic treatments likely work indirectly through the HPO axis. Many metabolic treatments have shown initial promise and later failed (troglitozone or d-chiro-inositol) or disappointed (metformin); further studies are needed of newer agents to treat type 2 diabetes. Weight loss interventions, lifestyle related, through obesity drugs or through bariatric surgery have shown mixed results on pregnancy outcomes. With both reproductive and metabolic treatments, combination therapies (such as metformin and clomiphene together) may offer greater benefit to distinct subgroups of patients.

8 Review The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. 2016

Balen, Adam H / Morley, Lara C / Misso, Marie / Franks, Stephen / Legro, Richard S / Wijeyaratne, Chandrika N / Stener-Victorin, Elisabet / Fauser, Bart C J M / Norman, Robert J / Teede, Helena. ·Leeds Centre for Reproductive Medicine, Leeds Teaching Hospitals, Leeds LS14 6UH, UK a.balen@nhs.net. · Leeds Centre for Reproductive Medicine, Leeds Teaching Hospitals, Leeds LS14 6UH, UK. · Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Monash Medical Centre, 43-51 Kanooka Grove, Clayton, VIC 3168, Australia. · Institute of Reproductive & Developmental Biology, Hammersmith Hospital, London, UK. · Penn State College of Medicine, 500 University Drive, H103, Hershey, PA 17033, USA. · Faculty of Medicine, University of Colombo, PO Box 271, Kynsey Road, Colombo 008, Sri Lanka. · Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. · Department of Reproductive Medicine & Gynaecology, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. · The Robinson Institute, University of Adelaide, Norwich House, 55 King William Street, North Adelaide, SA 5005, Australia. ·Hum Reprod Update · Pubmed #27511809.

ABSTRACT: BACKGROUND: Here we describe the consensus guideline methodology, summarise the evidence-based recommendations we provided to the World Health Organisation (WHO) for their consideration in the development of global guidance and present a narrative review on the management of anovulatory infertility in women with polycystic ovary syndrome (PCOS). OBJECTIVE AND RATIONALE: The aim of this paper was to present an evidence base for the management of anovulatory PCOS. SEARCH METHODS: The evidence to support providing recommendations involved a collaborative process for: (i) identification of priority questions and critical outcomes, (ii) retrieval of up-to-date evidence and exiting guidelines, (iii) assessment and synthesis of the evidence and (iv) the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation, the methodologist evaluated the quality of the supporting evidence that was then graded as very low, low, moderate or high for consideration during consensus. OUTCOMES: Evidence was synthesized and we made recommendations across the definition of PCOS including hyperandrogenism, menstrual cycle regulation and ovarian assessment. Metabolic features and the impact of ethnicity were covered. Management includes lifestyle changes, bariatric surgery, pharmacotherapy (including clomiphene citrate (CC), aromatase inhibitors, metformin and gonadotropins), as well as laparoscopic surgery. In-vitro fertilization (IVF) was considered as were the risks of ovulation induction and of pregnancy in PCOS. Approximately 80% of women who suffer from anovulatory infertility have PCOS. Lifestyle intervention is recommended first in women who are obese largely on the basis of general health benefits. Bariatric surgery can be considered where the body mass index (BMI) is ≥35 kg/m WIDER IMPLICATIONS: This guidance generation and evidence-synthesis analysis has been conducted in a manner to be considered for global applicability for the safe administration of ovulation induction for anovulatory women with PCOS.

9 Review Treatment strategies for infertile women with polycystic ovary syndrome. 2016

Vitek, Wendy / Hoeger, Kathleen / Legro, Richard S. ·Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY, USA - wendy_vitek@urmc.rochester.edu. ·Minerva Ginecol · Pubmed #26765152.

ABSTRACT: Polycystic ovary syndrome (PCOS) is a common reproductive disorder that can be diagnosed when two of the following three criteria are present: menstrual irregularity, hyperandrogenism and polycystic ovaries. Factors such as the individual's body weight influence the severity of the phenotype and risk of metabolic comorbidities. While anovulatory infertility is a common issue among lean and obese reproductive-aged women with PCOS, obesity is associated with resistance to oral ovulation induction agents, lower pregnancy rates and a higher risk of pregnancy complications. Lifestyle modification is recommended as first line therapy among obese women with PCOS in order to optimize their outcomes. Among lean and obese women with PCOS, ovulation induction can be achieved with aromatase inhibitors, selective estrogen receptor modulators, insulin sensitizing agents, gonadotropins and ovarian drilling with varying rates of ovulation, live birth and multiple gestations. Assisted reproductive technologies are reserved for women who do not conceive despite restoration of ovulation or couples with additional factors contributing to their infertility. This review will outline treatment strategies for achieving a healthy pregnancy among lean and obese women with PCOS and infertility.

10 Review The role of TGF-β in polycystic ovary syndrome. 2014

Raja-Khan, Nazia / Urbanek, Margrit / Rodgers, Raymond J / Legro, Richard S. ·1Division of Endocrinology, Diabetes, and Metabolism, Pennsylvania State University College of Medicine, M.S. Hershey Medical Center, Hershey, PA, USA. ·Reprod Sci · Pubmed #23585338.

ABSTRACT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligoanovulation and hyperandrogenism and associated with insulin resistance, type 2 diabetes, and cardiovascular risk. In recent years, genetic studies have linked PCOS to a dinucleotide marker D19S884 in the fibrillin 3 gene. Fibrillins make up the major component of microfibrils in the extracellular matrix (ECM) and interact with molecules in the ECM to regulate transforming growth factor β (TGF-β) signaling. Therefore, variations in fibrillin 3 and subsequent dysregulation of TGF-β may contribute to the pathogenesis of PCOS. Here, we review the evidence from genetic studies supporting the role of TGF-β in PCOS and describe how TGF-β dysregulation may contribute to (1) the fetal origins of PCOS, (2) reproductive abnormalities in PCOS, and (3) cardiovascular and metabolic abnormalities in PCOS.

11 Review Reproductive impact of polycystic ovary syndrome. 2012

Usadi, Rebecca S / Legro, Richard S. ·Center for Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Carolinas Medical Center, Charlotte, North Carolina, USA. Rebecca.Usadi@carolinashealthcare.org ·Curr Opin Endocrinol Diabetes Obes · Pubmed #23108198.

ABSTRACT: PURPOSE OF REVIEW: The purpose of this review is to highlight the impact of polycystic ovary syndrome (PCOS) on menstrual function, fertility and reproductive outcomes. Women with PCOS often present with anovulation, menstrual disturbances and hyperandrogenism. Management options for the reproductive disorders of PCOS will be discussed. RECENT FINDINGS: The role of metformin in treating PCOS is narrowing. New data show improved live birth rates by skipping a progestin withdrawal bleed and proceeding directly with a dose escalation of clomiphene for ovulation induction. The Pregnancy in PCOS trial II will determine the safety and efficacy of clomiphene citrate compared to letrozole, in achieving live birth in infertile women with PCOS. SUMMARY: Initial treatment for reproductive disorders in overweight and obese women with PCOS is weight loss. This helps menstrual disturbances, shortens the time to conception and reduces adverse obstetric risks. Clomiphene citrate is considered the first-line therapy for ovulatory infertility. Clomiphene citrate-resistant women may be offered aromatase inhibitors or laparoscopic ovarian surgery. Metformin does not improve live birth rate or reduce miscarriage rate and is no longer considered an option for ovulation induction. Women with PCOS need to be counseled about risks of multiple gestations with gonadotropin therapy.

12 Review Emerging concepts about prenatal genesis, aberrant metabolism and treatment paradigms in polycystic ovary syndrome. 2012

Witchel, Selma F / Recabarren, Sergio E / González, Frank / Diamanti-Kandarakis, Evanthia / Cheang, Kai I / Duleba, Antoni J / Legro, Richard S / Homburg, Roy / Pasquali, Renato / Lobo, Rogerio A / Zouboulis, Christos C / Kelestimur, Fahrettin / Fruzzetti, Franca / Futterweit, Walter / Norman, Robert J / Abbott, David H. ·Division of Pediatric Endocrinology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA. witchelsf@upmc.edu ·Endocrine · Pubmed #22661293.

ABSTRACT: The interactive nature of the 8th Annual Meeting of the Androgen Excess and PCOS Society Annual Meeting in Munich, Germany (AEPCOS 2010) and subsequent exchanges between speakers led to emerging concepts in PCOS regarding its genesis, metabolic dysfunction, and clinical treatment of inflammation, metabolic dysfunction, anovulation and hirsutism. Transition of care in congenital adrenal hyperplasia from pediatric to adult providers emerged as a potential model for care transition involving PCOS adolescents.

13 Review Polycystic ovary syndrome: current infertility management. 2011

Aubuchon, Mira / Legro, Richard S. ·Department of Obstetrics, Gynecology, and Women's Health, University of Missouri School of Medicine, Missouri Center for Reproductive Medicine and Fertility, Columbia, Missouri, USA. ·Clin Obstet Gynecol · Pubmed #22031257.

ABSTRACT: This review summarizes the diagnosis of polycystic ovary syndrome and management of associated infertility. The goal is to guide clinicians through basic evaluation, initial treatment, and briefly describe more complex therapies.

14 Review Incomplete and inconsistent reporting of maternal and fetal outcomes in infertility treatment trials. 2011

Dapuzzo, Lisa / Seitz, Faith E / Dodson, William C / Stetter, Christina / Kunselman, Allen R / Legro, Richard S. ·Department of Obstetrics and Gynecology, Lehigh Valley Hospital, Allentown, Pennsylvania, USA. ·Fertil Steril · Pubmed #21435640.

ABSTRACT: Pregnancy outcomes and adverse outcomes in infertility trials are reported to varying extents; for example, 35% of clinical trials reported no information on pregnancy loss, only 43% reported adverse events during the preconception treatment period, and only 7% reported any serious adverse events. Incomplete reporting limits the value of these studies in counseling patients on the risk-benefit ratio of treatment to themselves and their infants.

15 Clinical Trial Effect of Preconception Impaired Glucose Tolerance on Pregnancy Outcomes in Women With Polycystic Ovary Syndrome. 2017

Wei, Daimin / Zhang, Bo / Shi, Yuhua / Zhang, Lin / Zhao, Shigang / Du, Yanzhi / Xu, Lizhen / Legro, Richard S / Zhang, Heping / Chen, Zi-Jiang. ·Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250001, China. · Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China. · National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250001, China. · Center for Reproductive Medicine, Maternal and Child Health Hospital in Guangxi, Nanning 530003, China. · Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China. · Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, Pennsylvania 17033. · Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut 06520. ·J Clin Endocrinol Metab · Pubmed #28938429.

ABSTRACT: Context: Women with polycystic ovary syndrome (PCOS) commonly have intrinsic insulin resistance and are recommended to undergo an oral glucose tolerance test (OGTT) for diabetes screening. However, the effect of preconception impaired glucose tolerance (IGT) on pregnancy is still unclear. Objective: To prospectively assess the effect of preconception IGT on pregnancy outcomes. Design, Setting, Patients, Interventions, and Main Outcome Measures: This was a secondary analysis of a multicenter randomized trial in 1508 women with PCOS comparing live birth and obstetric complications between fresh and frozen embryo transfer. At baseline, fasting and 2-hour glucose and insulin levels after 75-g OGTT were measured. Results: Women with preconception IGT had higher risks of gestational diabetes in both singleton pregnancy [9.5% vs 3.2%; odds ratio (OR) 3.13; 95% confidence interval (CI) 1.23to 7.69] and twin pregnancy (20.0% vs 3.2%; OR 7.69; 95% CI 2.78 to 20.00) than women with normoglycemia. Preconception IGT was associated with a higher risk of large for gestational age in singleton newborns compared with normoglycemia (34.7% vs 19.8%; OR 2.13; 95% CI 1.19 to 3.85) or isolated impaired fasting glucose (i-IFG) (34.7% vs 15.4%; OR 2.94; 95% CI 1.33 to 6.25). Women with preconception IGT had a higher singleton pregnancy loss rate than women with i-IFG (31.4% vs 17.5%; OR 2.17; 95% CI 1.11 to 4.17). After adjusting for age, body mass index, duration of infertility, total testosterone level, and treatment groups (frozen vs fresh embryo transfer), these associations remained. Conclusions: Preconception IGT, independent from BMI, was associated with adverse pregnancy outcome compared with i-IFG and normoglycemia.

16 Clinical Trial Effects of gastric bypass surgery on female reproductive function. 2012

Legro, Richard S / Dodson, William C / Gnatuk, Carol L / Estes, Stephanie J / Kunselman, Allen R / Meadows, Juliana W / Kesner, James S / Krieg, Edward F / Rogers, Ann M / Haluck, Randy S / Cooney, Robert N. ·Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, 500 University Drive, H103, Hershey, Pennsylvania 17033, USA. rsl1@psu.edu ·J Clin Endocrinol Metab · Pubmed #23066115.

ABSTRACT: CONTEXT: Reproductive function may improve after bariatric surgery, although the mechanisms and time-related changes are unclear. OBJECTIVE: The objective of the study was to determine whether ovulation frequency/quality as well as associated reproductive parameters improve after Roux en Y gastric bypass surgery. DESIGN: This was a prospective cohort study that enrolled female subjects from 2005 to 2008 with study visits at baseline and then 1, 3, 6, 12, and up to 24 months after surgery. SETTING: The study was conducted at an academic health center. PATIENTS: Twenty-nine obese, reproductive-aged women not using confounding medications participated in the study. MAIN OUTCOME MEASURES: The primary outcome was integrated levels of urinary progestin (pregnanediol 3-glururonide) from daily urinary collections at 12 months postoperatively. Secondary outcomes were changes in vaginal bleeding, other biometric, hormonal, ultrasound, dual-energy x-ray absorptiometry measures, and Female Sexual Function Index. RESULTS: Ninety percent of patients with morbid obesity had ovulatory cycles at baseline, and the ovulatory frequency and luteal phase quality (based on integrated pregnanediol 3-glururonide levels) were not modified by bariatric surgery. The follicular phase was shorter postoperatively [6.5 d shorter at 3 months and 7.9-8.9 d shorter at 6-24 months (P < 0.01)]. Biochemical hyperandrogenism improved, largely due to an immediate postoperative increase in serum SHBG levels (P < 0.01), with no change in clinical hyperandrogenism (sebum production, acne, hirsutism). Bone density was preserved, contrasting with a significant loss of lean muscle mass and fat (P < 0.001), reflecting preferential abdominal fat loss (P < 0.001). Female sexual function improved 28% (P = 0.02) by 12 months. CONCLUSIONS: Ovulation persists despite morbid obesity and the changes from bypass surgery. Reproductive function after surgery is characterized by a shortened follicular phase and improved female sexual function.

17 Clinical Trial Increasing burden of institutional review in multicenter clinical trials of infertility: the Reproductive Medicine Network experience with the Pregnancy in Polycystic Ovary Syndrome (PPCOS) I and II studies. 2011

Schlaff, William D / Zhang, Heping / Diamond, Michael P / Coutifaris, Christos / Casson, Peter R / Brzyski, Robert G / Christman, Gregory M / Barnhart, Kurt T / Trussell, J C / Krawetz, Stephen A / Snyder, Peter J / Ohl, Dana / Santoro, Nanette / Eisenberg, Esther / Huang, Hao / Legro, Richard S / Anonymous5340696. ·Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Academic Office Building 1, 12631 E. 17th Avenue, Aurora, CO 80045, USA. william.schlaff@ucdenver.edu ·Fertil Steril · Pubmed #21645894.

ABSTRACT: CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00068861 and NCT00719186.

18 Article Comparison of sonohysterography to hysterosalpingogram for tubal patency assessment in a multicenter fertility treatment trial among women with polycystic ovary syndrome. 2018

Christianson, Mindy S / Legro, Richard S / Jin, Susan / Eisenberg, Esther / Diamond, Michael P / Hansen, Karl R / Vitek, Wendy / Styer, Aaron K / Casson, Peter / Coutifaris, Christos / Christman, Gregory M / Alvero, Ruben / Puscheck, Elizabeth E / Christy, Alicia Y / Sun, Fangbai / Zhang, Heping / Polotsky, Alex J / Santoro, Nanette. ·Department of Gynecology and Obstetrics, Division of Reproductive Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. mchris21@jhmi.edu. · Department of Ob/Gyn, Penn State College of Medicine, Hershey, PA, USA. · Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA. · Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. · Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, GA, USA. · Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. · Department of Obstetrics and Gynecology, University of Rochester School of Medicine, Rochester, NY, USA. · Department of Obstetrics, Gynecologyn, and Reproductive Biology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. · Department of Obstetrics and Gynecology, University of Vermont, Burlington, VT, USA. · Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA. · Department of Obstetrics and Gynecology, Shands Hospital, University of Florida, Gainesville, FL, USA. · Department of Obstetrics and Gynecology, Women and Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA. · Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. · Department of Obstetrics and Gynecology, University of Colorado, Aurora, CO, USA. ·J Assist Reprod Genet · Pubmed #30194618.

ABSTRACT: PURPOSE: To compare saline infusion sonohysterography (SIS) versus hysterosalpingogram (HSG) for confirmation of tubal patency. METHODS: Secondary analysis of a randomized controlled trial, Pregnancy in Polycystic Ovary Syndrome II (PPCOS II). Seven hundred fifty infertile women (18-40 years old) with polycystic ovary syndrome (PCOS) were randomized to up to 5 cycles of letrozole or clomiphene citrate. Prior to enrollment, tubal patency was determined by HSG, the presence of free fluid in the pelvis on SIS, laparoscopy, or recent intrauterine pregnancy. Logistic regression was conducted in patients who ovulated with clinical pregnancy as the outcome and HSG or SIS as the key independent variable. RESULTS: Among women who ovulated, 414 (66.9%) had tubal patency confirmed by SIS and 187 (30.2%) had at least one tube patent on HSG. Multivariable analysis indicated that choice of HSG versus SIS did not have a significant relationship on likelihood of clinical pregnancy, after adjustment for treatment arm, BMI, duration of infertility, smoking, and education (OR 1.14, 95% CI 0.77, 1.67, P = 0.52). Ectopic pregnancy occurred more often in women who had tubal patency confirmed by HSG compared to SIS (2.8% versus 0.6%, P = 0.02). CONCLUSIONS: In this large cohort of women with PCOS, there was no significant difference in clinical pregnancy rate between women who had tubal patency confirmed by HSG versus SIS. SIS is an acceptable imaging modality for assessment of tubal patency in this population.

19 Article Allostatic load, a measure of chronic physiological stress, is associated with pregnancy outcomes, but not fertility, among women with unexplained infertility. 2018

Barrett, Emily S / Vitek, Wendy / Mbowe, Omar / Thurston, Sally W / Legro, Richard S / Alvero, Ruben / Baker, Valerie / Bates, G Wright / Casson, Peter / Coutifaris, Christos / Eisenberg, Esther / Hansen, Karl / Krawetz, Stephen / Robinson, Randal / Rosen, Mitchell / Usadi, Rebecca / Zhang, Heping / Santoro, Nanette / Diamond, Michael. ·Department of Epidemiology, Environmental and Occupational Health Sciences Institute, Rutgers School of Public Health, 170 Frelinghuysen Road, Piscataway, NJ, USA. · Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY, USA. · Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, 265 Crittenden Avenue, Rochester, NY, USA. · Department of Obstetrics and Gynecology, Penn State University College of Medicine, 500 University Drive, Hershey, PA, USA. · Department of Obstetrics and Gynecology, Warren Alpert School of Medicine, Brown University, 90 Plain Street, Providence, RI, USA. · Department of Obstetrics and Gynecology, Stanford University School of Medicine, 1195 West Fremont Avenue, Sunnyvale, CA, USA. · Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 619 19th Street South, Birmingham, AL, USA. · Department of Obstetrics and Gynecology, University of Vermont, 111 Colchester Avenue, Burlington, VT, USA. · Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, 3701 Market Street, Philadelphia, PA, USA. · Fertility and Infertility Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, 6710B Rockledge Drive, Bethesda, MD, USA. · Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, 825 NE 10th Street, Oklahoma City, OK, USA. · Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 275 E. Hancock, Detroit, MI, USA. · Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, 8300 Floyd Curl Drive, San Antonio, TX, USA. · Department of Reproductive Endocrinology and Infertility, University of California, 550 16th Street, San Francisco, CA, USA. · Carolinas Health Care System, 1025 Morehead Medical Drive, Charlotte, NC, USA. · Yale School of Public Health, 300 George Street, New Haven, CT, USA. · Department of Obstetrics and Gynecology, University of Colorado, 12631 E 17th Avenue, Aurora, CO, USA. · Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, USA. ·Hum Reprod · Pubmed #30085177.

ABSTRACT: STUDY QUESTION: Among infertile women undergoing ovarian stimulation, is allostatic load (AL), a measure of chronic physiological stress, associated with subsequent fertility and pregnancy outcomes? SUMMARY ANSWER: AL at baseline was not associated with conception, spontaneous abortion or live birth, however, it was significantly associated with increased odds of pre-eclampsia and preterm birth among women who had a live birth in the study. WHAT IS KNOWN ALREADY: Several studies have linked AL during pregnancy to adverse outcomes including preterm birth and pre-eclampsia, hypothesizing that it may contribute to well-documented disparities in pregnancy and birth outcomes. However, AL biomarkers change over the course of pregnancy, raising questions as to whether gestational AL assessment is a valid measure of cumulative physiologic stress starting long before pregnancy. To better understand how AL may impact reproductive outcomes, AL measurement in the non-pregnant state (i.e. prior to conception) is needed. STUDY DESIGN, SIZE, DURATION: A secondary data analysis based on data from 836 women who participated in Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), a multi-center, randomized clinical trial of ovarian stimulation conducted from 2011 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovulatory women with unexplained infertility (ages 18-40) were enrolled and at baseline, biological and anthropometric measures were collected. AL scores were calculated as a composite of the following baseline variables determined a priori: BMI, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, dehydroepiandrosterone sulfate, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein and HOMA score. Participants received ovarian stimulation for up to four cycles and if they conceived, were followed throughout pregnancy. We fit multi-variable logistic regression models examining AL (one-tailed and two-tailed) in relation to the following reproductive outcomes: conception, spontaneous abortion, live birth, pre-eclampsia, preterm birth and low birthweight. MAIN RESULTS AND THE ROLE OF CHANCE: Adjusting for covariates, a unit increase in two-tailed AL score was associated with 62% increased odds of pre-eclampsia (OR: 1.62, 95% CI: 1.14, 2.38) 44% increased odds of preterm birth (OR: 1.44, 95% CI: 1.02, 2.08), and 39% increased odds of low birthweight (OR: 1.39, 95% CI: 0.99, 1.97). The relationship between AL and preterm birth was mediated by pre-eclampsia (P = 0.0003). In one-tailed AL analyses, associations were similar, but slightly attenuated. AL was not associated with fertility outcomes (conception, spontaneous abortion, live birth). LIMITATIONS, REASONS FOR CAUTION: Results may not be generalizable to fertile women who conceive naturally or women with other types of infertility. Comparisons to previous, related work are difficult because variables included in AL composite measures vary across studies. AL may be indicative of overall poor health, rather than being specific to chronic physiological stress. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that chronic physiological stress may not impact success of ovarian stimulation, however, they confirm and extend previous work suggesting that AL is associated with adverse pregnancy outcomes. Physiological dysregulation due to chronic stress has been proposed as a possible mechanism underlying disparities in birth outcomes, which are currently poorly understood. Assessing biomarkers of physiological dysregulation pre-conception or in early pregnancy, may help to identify women at risk of adverse pregnancy outcomes, particularly pre-eclampsia. STUDY FUNDING/COMPETING INTEREST(S): Support for AMIGOS was provided by: U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10HD055925. Support for the current analysis was provided by T32ES007271, R25HD075737, P30ES001247 and P30ES005022. This research was made possible by funding by American Recovery and Reinvestment Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of NICHD, NIEHS or NIH. E.B., W.V., O.M., R.A., M.R., V.B., G.W.B., C.C., E.E., S.K., R.U., P.C, H.Z., N.S. and S.T. have nothing to disclose. R.L. reported serving as a consultant to Abbvie, Bayer, Kindex, Odega, Millendo and Fractyl and serving as a site investigator and receiving grants from Ferring. K.H. reported receiving grants from Roche Diagnostics and Ferring. R.R. reported a grant from AbbVie. M.D. reported being on the Board of Directors of and a stockholder in Advanced Reproductive Care. TRIAL REGISTRATION NUMBER: Clinical Trials.gov number: NCT01044862.

20 Article Insulin resistance is associated with depression risk in polycystic ovary syndrome. 2018

Greenwood, Eleni A / Pasch, Lauri A / Cedars, Marcelle I / Legro, Richard S / Eisenberg, Esther / Huddleston, Heather G / Anonymous2551075. ·Department of Obstetrics, Gynecology and Reproductive Sciences, University of California-San Francisco, San Francisco, California. Electronic address: eleni.greenwood@ucsf.edu. · Department of Obstetrics, Gynecology and Reproductive Sciences, University of California-San Francisco, San Francisco, California. · Department of Obstetrics and Gynecology, Pennsylvania State University, Hershey, Pennsylvania. · Fertility and Infertility Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Maryland. ·Fertil Steril · Pubmed #29908775.

ABSTRACT: OBJECTIVE: To test the hypothesis that insulin resistance is associated with depression risk in polycystic ovary syndrome (PCOS). DESIGN: Secondary analysis of data from a multicenter randomized trial. SETTING: Multicenter university-based clinical practices. PATIENT(S): Seven hundred thirty-eight women with PCOS by modified Rotterdam criteria seeking pregnancy enrolled in a randomized clinical trial comparing clomiphene citrate versus letrozole. INTERVENTION(S): The Primary Care Evaluation of Mental Disorders Patient Health Questionnaire was self-administered to identify depression using a validated algorithm at enrollment. Demographic and anthropometric data were collected, and serum assays were performed. Insulin resistance was estimated using the homeostatic model of insulin resistance (HOMA-IR), with a cutoff of >2.2 considered abnormal. MAIN OUTCOME MEASURE(S): Demographic, endocrine, and metabolic parameters associated with depression. RESULT(S): In a univariate logistic regression analysis, elevated HOMA-IR was associated with 2.3-fold increased odds of depression (odds ratio [OR] = 2.32; 95% confidence interval [CI], 1.28-4.21). This association remained significant after controlling for age and body mass index (adjusted OR [aOR] = 2.23; 95% CI, 1.11-4.46) and in a model including additional potential confounders (aOR = 2.03; 95% CI, 1.00-4.16). CONCLUSION(S): Insulin resistance has a strong and independent association with depression in PCOS and may serve as a physiologic mediator. Our findings corroborate a growing body of evidence linking insulin resistance to depressed mood. The association between insulin resistance and depressed mood warrants further investigation to elucidate mechanisms and identify potential therapeutic targets.

21 Article Major depression, antidepressant use, and male and female fertility. 2018

Evans-Hoeker, Emily A / Eisenberg, Esther / Diamond, Michael P / Legro, Richard S / Alvero, Ruben / Coutifaris, Christos / Casson, Peter R / Christman, Gregory M / Hansen, Karl R / Zhang, Heping / Santoro, Nanette / Steiner, Anne Z / Anonymous2111140. ·Department of Obstetrics and Gynecology, Virginia Tech Carilion, Carilion Clinic, Roanoke, Virginia. Electronic address: eaevanshoeker@carilionclinic.org. · Fertility and Infertility Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Maryland. · Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia. · Department of Obstetrics and Gynecology, Pennsylvania State University, Hershey, Pennsylvania. · Department of Obstetrics and Gynecology, University of Colorado, Denver, Colorado. · Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. · Department of Obstetrics and Gynecology, University of Vermont, Burlington, Vermont. · Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan. · Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma. · Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut. · Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina. ·Fertil Steril · Pubmed #29778387.

ABSTRACT: OBJECTIVE: To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments. DESIGN: Cohort study. SETTING: Clinics. PATIENT(S): Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility). INTERVENTION(S): Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD. MAIN OUTCOME MEASURE(S): Primary outcome: live birth. SECONDARY OUTCOMES: pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS). RESULT(S): Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception. CONCLUSION(S): Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant. CLINICAL TRIAL REGISTRATION NUMBERS: NCT00719186 and NCT01044862.

22 Article Midluteal Progesterone: A Marker of Treatment Outcomes in Couples With Unexplained Infertility. 2018

Hansen, Karl R / Eisenberg, Esther / Baker, Valerie / Hill, Micah J / Chen, Sixia / Talken, Sara / Diamond, Michael P / Legro, Richard S / Coutifaris, Christos / Alvero, Ruben / Robinson, Randal D / Casson, Peter / Christman, Gregory M / Santoro, Nanette / Zhang, Heping / Wild, Robert A / Anonymous8371104. ·Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland. · Department of Obstetrics and Gynecology, Stanford University, Sunnyvale, California. · Reproductive Endocrinology and Infertility Fellowship, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. · Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan. · Department of Obstetrics and Gynecology, Pennsylvania State University, Hershey, Pennsylvania. · Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Obstetrics and Gynecology, University of Colorado Denver, Aurora, Colorado. · Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. · Department of Obstetrics and Gynecology, University of Vermont, Burlington, Vermont. · Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan. · Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut. ·J Clin Endocrinol Metab · Pubmed #29767754.

ABSTRACT: Context: Adequate luteal phase progesterone exposure is necessary to induce endometrial changes required for a successful pregnancy outcome. The relationship between low midluteal progesterone concentration and the outcome of live birth in ovarian stimulation with intrauterine insemination (OS-IUI) treatments is not defined. Objective: To determine the level of midluteal progesterone portending a low chance of live birth after OS-IUI in couples with unexplained infertility. Design and Setting: Secondary analyses of data from a prospective, randomized, multicenter clinical trial that determined pregnancy outcomes following OS-IUI with clomiphene citrate, letrozole, or gonadotropins for couples with unexplained infertility. Participants: Couples (n = 900) underwent 2376 OS-IUI cycles during the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial. Main Outcome Measures: Live birth as it relates to midluteal progesterone level and thresholds below which no live births occur by treatment group. Results: Thresholds for non-live birth cycles were similar for clomiphene (14.4 ng/mL) and letrozole (13.1 ng/mL) yet were lower for gonadotropin (4.3 ng/mL) treatments. A midluteal progesterone level >10th percentile specific for each treatment group independently was associated with greater odds for a live birth in all OS-IUI cycles (adjusted OR: 2.17; 95% CI: 1.05, 4.48). Conclusions: During OS-IUI, a low midluteal progesterone level was associated with a low probability of live birth. Thresholds differed by medication, with the lowest threshold for gonadotropin. Several pathophysiologic mechanisms may account for low progesterone levels. Refinement of the predictive range associated with particular ovarian stimulation medications during treatment of unexplained infertility may improve accuracy.

23 Article Obstetric complications after frozen versus fresh embryo transfer in women with polycystic ovary syndrome: results from a randomized trial. 2018

Zhang, Bo / Wei, Daimin / Legro, Richard S / Shi, Yuhua / Li, Jing / Zhang, Lin / Hong, Yan / Sun, Gang / Zhang, Ting / Li, Weiping / Chen, Zi-Jiang. ·Center for Reproductive Medicine, Maternal and Child Health Hospital in Guangxi, Nanning, People's Republic of China. · Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China; The Key Laboratory of Reproductive Endocrinology of Ministry of Education, and National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, People's Republic of China. · Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, Pennsylvania. · Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai, People's Republic of China. · Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China; The Key Laboratory of Reproductive Endocrinology of Ministry of Education, and National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, People's Republic of China; Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai, People's Republic of China. Electronic address: chenzijiang@hotmail.com. ·Fertil Steril · Pubmed #29338857.

ABSTRACT: OBJECTIVE: To evaluate the effect of frozen embryo transfer on maternal and neonatal complications of singleton and twin pregnancies compared with fresh embryo transfer in women with polycystic ovary syndrome (PCOS). DESIGN: A secondary analysis of a multicenter, randomized, controlled trial comparing live birth after frozen vs. fresh embryo transfer (FreFro-PCOS). SETTING: Reproductive medicine centers. PATIENT(S): A total of 1,508 patients with a diagnosis of PCOS who were undergoing IVF were enrolled. INTERVENTION(S): On day of oocyte retrieval, eligible patients were randomized to the fresh or frozen embryo transfer groups. Up to two embryos were transferred in both groups. All pregnancies were followed up until delivery. MAIN OUTCOME MEASURE(S): Gestational diabetes mellitus, pre-eclampsia, preterm birth, small for gestational age, and large for gestational age. RESULT(S): The risks of gestational diabetes mellitus, preterm birth, and small for gestational age were comparable between the frozen and fresh embryo transfer groups in both singleton and twin births. However, singleton infants born after frozen embryo transfer were more likely to be large for gestational age (25.2% vs. 17.5%; relative risk 1.44, 95% confidence interval 1.01-2.07, P=.044) than those born after fresh embryo transfer. Twin pregnancy after frozen embryo transfer had a higher risk of pre-eclampsia (12.0% vs. 2.8%; relative risk 4.31, 95% confidence interval 1.27-14.58, P=.009) than those after fresh embryo transfer. CONCLUSION(S): In women with PCOS, frozen embryo transfer resulted in an increased risk of large for gestational age in singleton pregnancy and a higher risk of pre-eclampsia in twin pregnancy. CLINICAL TRIAL REGISTRATION NUMBER: NCT01841528.

24 Article Transfer of Fresh versus Frozen Embryos in Ovulatory Women. 2018

Shi, Yuhua / Sun, Yun / Hao, Cuifang / Zhang, Heping / Wei, Daimin / Zhang, Yunshan / Zhu, Yimin / Deng, Xiaohui / Qi, Xiujuan / Li, Hong / Ma, Xiang / Ren, Haiqin / Wang, Yaqin / Zhang, Dan / Wang, Bo / Liu, Fenghua / Wu, Qiongfang / Wang, Ze / Bai, Haiyan / Li, Yuan / Zhou, Yi / Sun, Mei / Liu, Hong / Li, Jing / Zhang, Lin / Chen, Xiaoli / Zhang, Songying / Sun, Xiaoxi / Legro, Richard S / Chen, Zi-Jiang. ·From the Center for Reproductive Medicine, Shandong Provincial Hospital-Shandong University, the Key Laboratory of Reproductive Endocrinology of Ministry of Education, and the National Research Center for Assisted Reproductive Technology and Reproductive Genetics (Y. Shi, D.W., Z.W., M.S. H. Liu, J.L., L.Z., Z.-J.C.), and the Center for Reproductive Medicine, Qilu Hospital of Shandong University (X.D.), Jinan, the Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, and Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics (Y. Sun, Z.-J.C.), and the Shanghai Jiai Genetic and IVF Center, Obstetrics and Gynecology Hospital, Fudan University (X.S.), Shanghai, the Center for Reproductive Medicine of Yantai Yuhuangding Hospital, Yantai (C.H.), the Center for Reproductive Medicine, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin (Y. Zhang), the Department of Reproductive Endocrinology, Women's Hospital (Y. Zhu, D.Z.), and the Center for Reproductive Medicine (S.Z.), School of Medicine, Zhejiang University, Hangzhou, the Affiliated Hospital of Qingdao University (X.Q.) and the Center for Reproductive Medicine, Qingdao Women and Children's Hospital-Qingdao University (Y. Zhou), Qingdao, the Center for Reproduction and Genetics, Suzhou Municipal Hospital, Suzhou (H. Li), the Department of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical University-Jiangsu Province Hospital, Nanjing, (X.M.), the Reproductive Medicine Center of Jinghua Hospital, Shenyang (H.R.), the Center for Reproductive Medicine, Wuhan University, Wuhan (Y.W.), the Reproductive Medicine Research Center, 6th Affiliated Hospital of Sun Yat-sen University (B.W.), the Center for Reproductive Medicine, Women and Children's Hospital of Guangdong Province (F.L.), and the Center for Reproductive Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University (X.C.), Guangzhou, the Center for Reproductive Medicine, Maternal and Child Health Care Hospital of Jiangxi Province, Nanchang (Q.W.), the Center for Assisted Reproduction, Northwest Women and Children's Hospital, Xi'an (H.B.), and the Center for Reproductive Medicine, Beijing Chaoyang Hospital, Beijing (Y.L.) - all in China · the Department of Biostatistics, Yale University School of Public Health, New Haven, CT (H.Z.) · and the Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, PA (R.S.L.). ·N Engl J Med · Pubmed #29320646.

ABSTRACT: BACKGROUND: Elective frozen-embryo transfer has been shown to result in a higher live-birth rate than fresh-embryo transfer among anovulatory women with the polycystic ovary syndrome. It is uncertain whether frozen-embryo transfer increases live-birth rates among ovulatory women with infertility. METHODS: In this multicenter, randomized trial, we randomly assigned 2157 women who were undergoing their first in vitro fertilization cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. Up to two cleavage-stage embryos were transferred in each participant. The primary outcome was a live birth after the first embryo transfer. RESULTS: The live-birth rate did not differ significantly between the frozen-embryo group and the fresh-embryo group (48.7% and 50.2%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.89 to 1.06; P=0.50). There were also no significant between-group differences in the rates of implantation, clinical pregnancy, overall pregnancy loss, and ongoing pregnancy. Frozen-embryo transfer resulted in a significantly lower risk of the ovarian hyperstimulation syndrome than fresh-embryo transfer (0.6% vs. 2.0%; relative risk, 0.32; 95% CI, 0.14 to 0.74; P=0.005). The risks of obstetrical and neonatal complications and other adverse outcomes did not differ significantly between the two groups. CONCLUSIONS: The live-birth rate did not differ significantly between fresh-embryo transfer and frozen-embryo transfer among ovulatory women with infertility, but frozen-embryo transfer resulted in a lower risk of the ovarian hyperstimulation syndrome. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China; Chinese Clinical Trial Registry number, ChiCTR-IOR-14005406 .).

25 Article Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial. 2017

Wu, Xiao-Ke / Stener-Victorin, Elisabet / Kuang, Hong-Ying / Ma, Hong-Li / Gao, Jing-Shu / Xie, Liang-Zhen / Hou, Li-Hui / Hu, Zhen-Xing / Shao, Xiao-Guang / Ge, Jun / Zhang, Jin-Feng / Xue, Hui-Ying / Xu, Xiao-Feng / Liang, Rui-Ning / Ma, Hong-Xia / Yang, Hong-Wei / Li, Wei-Li / Huang, Dong-Mei / Sun, Yun / Hao, Cui-Fang / Du, Shao-Min / Yang, Zheng-Wang / Wang, Xin / Yan, Ying / Chen, Xiu-Hua / Fu, Ping / Ding, Cai-Fei / Gao, Ya-Qin / Zhou, Zhong-Ming / Wang, Chi Chiu / Wu, Tai-Xiang / Liu, Jian-Ping / Ng, Ernest H Y / Legro, Richard S / Zhang, Heping / Anonymous3251076. ·Committee of Reproductive Medicine, World Federation of Chinese Medicine Societies, Beijing, China2Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China. · Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China3Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. · Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China. · Outpatient Department, Xuzhou Maternal and Children's Hospital, Xuzhou, China. · Centre for Reproductive Medicine, Dalian Maternal and Children's Centre, Dalian, China. · Department of Infertility, Tanggu District Maternal and Children's Hospital, Tianjin, China. · Department of Obstetrics and Gynecology, Shanxi Province Hospital of Chinese Medicine, Taiyuan, China. · Centre for Reproductive Medicine, Huaian Maternal and Children's Hospital, Huaian, China. · Department of Gynecology, Suzhou City Hospital of Chinese Medicine, Suzhou, China. · Department of Gynecology, Second Hospital, Jiangxi University of Chinese Medicine, Nanchang, China. · Department of Chinese Medicine, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. · Department of Infertility, Liwan District Hospital of Chinese Medicine, Guangzhou, China. · Department of Obstetrics and Gynecology, Affiliated Hospital, Anhui University of Chinese Medicine, Hefei, China. · Institute of Integrated Traditional and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Gynecology, Wenzhou City Hospital of Chinese Medicine, Wenzhou, China. · Centre for Reproductive Medicine, Yuhuangding Hospital, Yantai, China. · Department of Obstetrics and Gynecology, Daqing Longnan Hospital, Daqing, China. · Department of Obstetrics and Gynecology, First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, China. · Department of Obstetrics and Gynecology, First Affiliated Hospital, Liaoning University of Chinese Medicine, Shenyang, China. · Department of Gynecology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China. · Department of Traditional Technology, Guangdong Province Hospital of Chinese Medicine, Guangzhou, China. · Department of Gynecology, Hangzhou City Hospital of Chinese Medicine, Hangzhou, China. · Centre for Reproductive Medicine, Zhejiang Province Hospital of Integrative Medicine, Hangzhou, China. · Centre for Reproductive Medicine, Daqing Oilfield General Hospital, Daqing, China. · Department of Obstetrics and Gynecology, Hubei Province Hospital of Chinese Medicine, Wuhan, China. · Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Hong Kong, China27Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China28School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China. · Chinese Clinical Trial Registry, Shenzhen, China. · Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. · Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong, China. · Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China32Department of Obstetrics and Gynecology, Pennsylvania State University, Hershey. · Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut. ·JAMA · Pubmed #28655015.

ABSTRACT: Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

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