Richard S Legro

Pennsylvania State University, University Park, Maryland, United States

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Publications (276)1341.68 Total impact

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    ABSTRACT: Obese men with normal semen parameters exhibit reduced fertility but few prospective data are available. To determine the impact of male factors and body mass among the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) participants. This is a secondary analysis of the PPCOS II trial. 750 infertile women with PCOS were randomized to up to 5 cycles of letrozole or clomiphene citrate. Females were 18-39 years old and had a male partner with sperm concentration of at least 14 million/mL who consented to regular intercourse. Analysis was limited to couples with complete male partner information (n=710). Male BMI was higher in couples who failed to conceive (29.5 kg/m(2) vs. 28.2 kg/m(2), p=0.039) as well as those who did not achieve a live birth (29.5 kg/m(2) vs. 28.1 kg/m(2), p=0.047). At least one partner was obese in 548 couples, 77.1%. A total of 261 couples were concordant for obesity (36.8%). After adjustment for female BMI, the association of male BMI with live birth was no longer significant (OR= 0.85, 95 % CI: 0.68-1.05, p=0.13). Couples where both partners smoked had a lower chance of live birth vs. non-smokers (OR= 0.20, 95 % CI: 0.08-0.52, p=0.02), whereas there was not a significant effect of female or male smoking alone. Live birth was more likely in couples with at least 3 sexual intercourse attempts over the previous 4 weeks (reported at baseline) as opposed to couples with lesser frequency (OR= 4.39, 95 % CI: 1.52-12.4, p<0.01). In this large cohort of obese women with PCOS, impact of male obesity was explained by female BMI. Lower chance of success was seen among couples where both partners smoked. Obesity and smoking are common among women with PCOS and their partners and contribute to a decrease in fertility treatment success.
    The Journal of Clinical Endocrinology and Metabolism 04/2015; DOI:10.1210/jc.2015-1178 · 6.31 Impact Factor
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    ABSTRACT: To determine if the intrapartum use of a 5% glucose-containing intravenous solution decreases the chance of a cesarean delivery for women presenting in active labor. This was a multi-center, prospective, single (patient) blind, randomized study design implemented at 4 obstetric residency programs in Pennsylvania. Singleton, term, consenting women presenting in active spontaneous labor with a cervical dilation of <6cm were randomized to lactated Ringer's with or without 5% glucose (LR versus D5LR) as their maintenance intravenous fluid. The primary outcome was the cesarean birth rate. Secondary outcomes included labor characteristics, as well as maternal or neonatal complications. There were 309 women analyzed. Demographic variables and admitting cervical dilation were similar among study groups. There was no significant difference in the cesarean delivery rate for the D5LR group (23/153 or 15.0%) versus the LR arm (18/156 or 11.5%), [RR (95%CI) of 1.32 (0.75, 2.35), P=0.34]. There were no differences in augmentation rates or intrapartum complications. The use of intravenous fluid containing 5% dextrose does not lower the chance of cesarean delivery for women admitted in active labor.
  • Richard S Legro
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    ABSTRACT: This Views and Reviews article examines FDA-approved uses of prescription drugs, as well as common off-label uses of drugs for several disorders that are frequently seen in reproductive medicine. Off-label drug use is ubiquitous in reproductive medicine, a fact that may be related to the disincentives to formally study these drugs in a potentially vulnerable population (i.e., pregnant women). It behooves clinicians to discuss with patients the risk-benefit ratio of treatment, and whether a treatment is FDA-approved for that condition. Researchers, seeking better data on effects of these drugs, may find fodder for future clinical studies in these articles. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
  • Richard S Legro
    Seminars in Reproductive Medicine 03/2015; 33(2):61-2. DOI:10.1055/s-0035-1546425 · 3.00 Impact Factor
  • Richard S. Legro
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    ABSTRACT: To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. Randomized, prospective clinical trial. Multicenter university-based clinical practices. A total of 900 couples with unexplained infertility. Collection of baseline demographics, blood samples, and ultrasonographic assessments. Demographic, laboratory, imaging, and survey characteristics. Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment. NCT 01044862. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    Fertility and Sterility 02/2015; DOI:10.1016/j.fertnstert.2014.12.130 · 4.30 Impact Factor
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    ABSTRACT: Mindfulness-based stress reduction (MBSR) may be beneficial for overweight/obese women, including women with polycystic ovary syndrome (PCOS), as it has been shown to reduce psychological distress and improve quality of life in other patient populations. Preliminary studies suggest that MBSR may also have salutary effects on blood pressure and blood glucose. This paper describes the design and methods of an ongoing pilot randomized controlled trial evaluating the feasibility and effects of MBSR in PCOS and non-PCOS women who are overweight or obese. Eighty six (86) women with body mass index ≥25kg/m(2), including 31 women with PCOS, have been randomized to 8weeks of MBSR or health education control, and followed for 16weeks. The primary outcome is mindfulness assessed with the Toronto Mindfulness Scale. Secondary outcomes include measures of blood pressure, blood glucose, quality of life, anxiety and depression. Our overall hypothesis is that MBSR will increase mindfulness and ultimately lead to favorable changes in blood pressure, blood glucose, psychological distress and quality of life in PCOS and non-PCOS women. This would support the integration of MBSR with conventional medical treatments to reduce psychological distress, cardiovascular disease and diabetes in PCOS and non-PCOS women who are overweight or obese. Copyright © 2015 Elsevier Inc. All rights reserved.
    Contemporary Clinical Trials 02/2015; 41. DOI:10.1016/j.cct.2015.01.021 · 1.99 Impact Factor
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a strong heritable component based on familial clustering and twin studies. Genome-wide association studies (GWAS) identified several PCOS candidate loci including LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A. We propose that these candidates comprise a hierarchical signaling network by which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream signaling cascades converge to regulate theca cell androgen biosynthesis. Future elucidation of the functional gene networks predicted by the PCOS GWAS will result in new diagnostic and therapeutic approaches for women with PCOS. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Trends in Endocrinology and Metabolism 01/2015; DOI:10.1016/j.tem.2014.12.004 · 8.87 Impact Factor
  • Richard S Legro
    Seminars in Reproductive Medicine 01/2015; 33(1):1-2. DOI:10.1055/s-0034-1395270 · 3.00 Impact Factor
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    ABSTRACT: Context: Although inflammation is clearly associated with obesity, diabetes, and insulin resistance, the role of chronic inflammation in the etiology of PCOS is unclear. Objective: To determine whether chronic inflammation plays a causal role in the etiology of PCOS, we tested for association between PCOS and genetic markers mapping to 80 members of the inflammatory pathway. Design: Case-control association study. Setting: Academic medical center. Patients or Participants: 905 index cases with PCOS and 955 control women (108 intensively-phenotyped subjects with normal androgen levels and regular menses and 847 minimally-phenotyped subjects with regular menses and no history of PCOS). Interventions: Subjects were genotyped at SNPs mapping to 80 inflammatory genes. Logistic regression was used to test for association between 822 SNPs and PCOS after adjusting for population stratification, BMI and/or age. In the index cases, we also tested for association with 11 quantitative traits (BMI, testosterone, fasting insulin, fasting glucose, 2-hour post-challenge glucose, LH, FSH, total cholesterol, HDL, LDL and triglyceride levels). Main Outcome Measures: Evidence for association with PCOS and with 11 quantitative traits. Results: Nominally significant evidence for association was observed with MAP3K7, IKBKG, TNFRS11A, AKT2, IL6R and IRF1, but none remained statistically significant after adjustment for multiple testing. Conclusions: Genetic variation in the inflammatory pathway is not a major contributor to the etiology of PCOS or related quantitative traits in women with PCOS.
    The Journal of Clinical Endocrinology and Metabolism 12/2014; 99(3):jc20132342. DOI:10.1210/jc.2013-2342 · 6.31 Impact Factor
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  • Richard S Legro
    Seminars in Reproductive Medicine 11/2014; 32(6):417-418. DOI:10.1055/s-0034-1384623 · 3.00 Impact Factor
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    ABSTRACT: The aim of this prospective cohort study was to determine the time-course in androgen and semen parameters in men after weight loss associated with bariatric surgery. Six men aged 18–40 years, meeting National Institutes of Health bariatric surgery guidelines, were followed between 2005 and 2008. Study visits took place at baseline, then 1, 3, 6 and 12 months after surgery. All men underwent Roux-en-y gastric bypass (RYGB). At each visit, biometric, questionnaire, serum, and urinary specimens and seman analysis were collected. Urinary integrated total testosterone levels increased significantly (P < 0.0001) by 3 months after surgery, and remained elevated throughout the study. Circulating testosterone levels were also higher at 1 and 6 months after surgery, compared with baseline. Serum sex hormone-binding globulin levels were significantly elevated at all time points after surgery (P < 0.01 to P = 0.02). After RYGB surgery, no significant changes occurred in urinary oestrogen metabolites (oestrone 3-glucuronide), serum oestradiol levels, serial semen parameters or male sexual function by questionnaire. A threshold of weight loss is necessary to improve male reproductive function by reversing male hypogonadism, manifested as increased testosterone levels. Further serial semen analyses showed normal ranges for most parameters despite massive weight loss.
    Reproductive biomedicine online 11/2014; 30(2). DOI:10.1016/j.rbmo.2014.10.014 · 2.98 Impact Factor
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    ABSTRACT: We assessed the impact of energy deficiency on menstrual function using controlled feeding and supervised exercise over four menstrual cycles (1 Baseline and 3 Intervention cycles) in untrained, eumenorrheic women ages 18-30 yrs. Subjects were randomized to either an exercising control (EXCON) or one of three exercising energy deficit (ED) groups i.e., mild (ED1) (-8 ± 2%), moderate (ED2) (-22 ± 3%), or severe (ED3) (-42 ± 3%). Menstrual cycle length and changes in urinary concentrations of estrone-1-glucuronide, pregnanediol glucuronide, and mid-cycle luteinizing hormone were assessed. Thirty-four subjects completed the study. Weight loss occurred in ED1 (- 3.8 ± 0.2 kg), ED2 (- 2.8 ± 0.6 kg), and ED3 (- 2.6 ± 1.1 kg), but was minimal in EXCON (-0.9 ± 0.7 kg). The overall sum of disturbances (luteal phase defects, anovulation, and oligomenorrhea) was greater in ED2 compared to EXCON and greater in ED3 compared to EXCON AND ED1. The average percent energy deficit was the main predictor of the frequency of menstrual disturbances (f = 10.1; β= -0.48; R2=0.23; p=0.003) even when including weight loss in the model. The estimates of the magnitude of energy deficiency associated with menstrual disturbances ranged from -22% (ED2) to -42% (ED3), reflecting an energy deficit of -470 to -810 kcal per day, respectively. This is the first study to demonstrate a dose response relation between the magnitude of energy deficiency and the frequency of exercise-related menstrual disturbances; however, the severity of menstrual disturbances was not dependent on the magnitude of energy deficiency.
    AJP Endocrinology and Metabolism 10/2014; DOI:10.1152/ajpendo.00386.2013 · 4.09 Impact Factor
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    ABSTRACT: Are there abnormalities in gonadotrophin secretion, adrenal steroidogenesis and/or testicular steroidogenesis in brothers of women with polycystic ovary syndrome (PCOS)?
    Human Reproduction 10/2014; 29(12). DOI:10.1093/humrep/deu282 · 4.59 Impact Factor
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    ABSTRACT: Do women with polycystic ovary syndrome (PCOS) seeking fertility treatment report smoking accurately and does participation in infertility treatment alter smoking?
    Human Reproduction 10/2014; 29(12). DOI:10.1093/humrep/deu239 · 4.59 Impact Factor
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    ABSTRACT: Context: Two genome wide association studies (GWAS) of PCOS have identified 11 susceptibility loci in Chinese individuals. Some of the risk loci identified in Chinese cohorts, mostly from the first GWAS, have been replicated in Europeans. Replication of the loci from the second GWAS in European cohorts is necessary to determine whether the same variants confer risk for PCOS in multiple ethnicities. Objective: To determine the effects of the Chinese GWAS loci in European-origin individuals. Design: Genetic association study. Setting: Tertiary care academic center. Patients: Eight hundred and forty-five European subjects with PCOS and 845 controls. Interventions: Blood sampling and genotyping. Main Outcome Measure: The association between PCOS and 12 independent single nucleotide polymorphisms (SNPs) mapping to 7 of the Chinese GWAS loci in a European cohort. Results: Variants in DENND1A (P=0.0002), THADA (P=0.035), FSHR (P=0.007) and INSR (P=0.046) were associated with PCOS in Europeans. The genetic risk score, generated for each subject based on the total number of risk alleles, was associated with the diagnosis of PCOS (P<0.0001), and remained associated (P=0.02) even after exclusion of the four variants individually associated with PCOS. Conclusions: At least four of the PCOS susceptibility loci identified in the Chinese GWAS are associated with PCOS in Europeans. The overall genetic burden for PCOS, as demonstrated by the risk score, is also associated with the diagnosis of PCOS in Europeans. The PCOS susceptibility loci identified in the Chinese GWAS are thus likely to play an important role in the etiology of PCOS across ethnicities.
    Journal of Clinical Endocrinology &amp Metabolism 10/2014; 100(1):jc20142689. DOI:10.1210/jc.2014-2689 · 6.31 Impact Factor
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    ABSTRACT: Clinical trials testing infertility treatments often do not report on the major outcomes of interest to patients and clinicians and the public (such as live birth) nor on the harms, including maternal risks during pregnancy and fetal anomalies. This is complicated by the multiple participants in infertility trials which may include a woman (mother), a man (father), and result in a third individual if successful, their offspring (child), who is also the desired outcome of treatment. The primary outcome of interest and many adverse events occur after cessation of infertility treatment and during pregnancy and the puerperium, which create a unique burden of follow-up for clinical trial investigators and participants. In 2013, because of the inconsistencies in trial reporting and the unique aspects of infertility trials not adequately addressed by existing Consolidated Standards of Reporting Trials (CONSORT) statements, we convened a consensus conference in Harbin, China, with the aim of planning modifications to the CONSORT checklist to improve the quality of reporting of clinical trials testing infertility treatment. The consensus group recommended that the preferred primary outcome of all infertility trials is live birth (defined as any delivery of a live infant ≥20 weeks gestations) or cumulative live birth, defined as the live birth per women over a defined time period (or number of treatment cycles). In addition, harms to all participants should be systematically collected and reported, including during the intervention, any resulting pregnancy, and during the neonatal period. Routine information should be collected and reported on both male and female participants in the trial. We propose to track the change in quality that these guidelines may produce in published trials testing infertility treatments. Our ultimate goal is to increase the transparency of benefits and risks of infertility treatments to provide better medical care to affected individuals and couples.
    Fertility and Sterility 09/2014; 102(4). DOI:10.1093/humrep/deu218 · 4.30 Impact Factor
  • Fertility and Sterility 09/2014; 102(3):e2. DOI:10.1016/j.fertnstert.2014.07.014 · 4.30 Impact Factor
  • Fertility and Sterility 09/2014; 102(3):e247. DOI:10.1016/j.fertnstert.2014.07.841 · 4.30 Impact Factor

Publication Stats

11k Citations
1,341.68 Total Impact Points

Institutions

  • 2000–2015
    • Pennsylvania State University
      University Park, Maryland, United States
    • University of California, Los Angeles
      • Department of Obstetrics and Gynecology
      Los Angeles, California, United States
  • 1995–2015
    • Penn State Hershey Medical Center and Penn State College of Medicine
      • • Obstetrics and Gynecology
      • • Cellular and Molecular Physiology
      • • Department of Medicine
      Hershey, Pennsylvania, United States
    • Magee-Womens Hospital
      Pittsburgh, Pennsylvania, United States
  • 2014
    • Heilongjiang University of Chinese Medicine
      Charbin, Heilongjiang Sheng, China
  • 2004–2013
    • William Penn University
      Hershey, Pennsylvania, United States
  • 2012
    • Carolinas Medical Center University
      Charlotte, North Carolina, United States
  • 2007–2012
    • Duke University
      Durham, North Carolina, United States
  • 2005–2012
    • University of Alabama at Birmingham
      • Department of Obstetrics and Gynecology
      Birmingham, Alabama, United States
  • 2003–2009
    • Northwestern University
      • Division of Endocrinology, Metabolism and Molecular Medicine
      Evanston, IL, United States
  • 2006
    • Università degli Studi di Palermo
      Palermo, Sicily, Italy
  • 1998–2005
    • Brigham and Women's Hospital
      • • Division of Endocrinology, Diabetes and Hypertension
      • • Division of Women’s Health
      Boston, Massachusetts, United States
  • 2000–2004
    • University of Pennsylvania
      • Department of Genetics
      Philadelphia, Pennsylvania, United States
  • 2002
    • Massachusetts General Hospital
      • Department of Obstetrics and Gynecology
      Boston, Massachusetts, United States
  • 2000–2002
    • West Georgia Obstetrics and Gynecology
      Georgetown, Georgia, United States
  • 1993–1995
    • University of Southern California
      • Department of Obstetrics and Gynecology
      Los Angeles, CA, United States
  • 1994
    • Women & Infants Hospital
      Providence, Rhode Island, United States