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    Waist circumference in relation to outcomes of infertility treatment with assisted reproductive technologies. Li Ming-Chieh,Mínguez-Alarcón Lidia,Arvizu Mariel,Chiu Yu-Han,Ford Jennifer B,Williams Paige L,Attaman Jill,Hauser Russ,Chavarro Jorge E, American journal of obstetrics and gynecology BACKGROUND:Many studies have documented a lower likelihood of live birth with increasing body mass index among women undergoing assisted reproductive technology, but few have examined the association with waist circumference, an anthropometric measure that allows assessment of central adiposity. OBJECTIVE:To examine the relation between baseline waist circumference and infertility treatment outcomes among women undergoing treatment with assisted reproductive technology. MATERIALS AND METHODS:We followed up 264 women who underwent 445 assisted reproductive technology cycles for infertility treatment at the Massachusetts General Hospital between 2010 and 2017. Waist circumference was assessed at enrollment. We used cluster-weighted generalized estimating equation models to estimate the probability of live birth by tertiles of waist circumference (<77, 77-86, >86 cm), while accounting for multiple treatment cycles per woman and adjusting for age, race, smoking, infertility diagnosis, day 3 follicle-stimulating hormone, body mass index, and height. RESULTS:Mean (standard deviation) waist circumference and body mass index were 83.6 (12.6) cm and 24.1 (4.3) kg/m, respectively. Waist circumference and body mass index were positively correlated (r = 0.69, P < .0001). Waist circumference was inversely related to the probability of live birth after adjusting for BMI and other confounders. The multivariable adjusted probability of live birth (95% confidence interval) for women in increasing tertiles of waist circumference were 53% (42-65%), 42% (32-53%), and 38% (28-50%) (P, trend = .04). When women were classified in joint categories of body mass index and waist circumference, women with a body mass index ≥25 kg/m and a waist circumference ≥77 cm had the lowest live birth rate (38% [27-50%]), whereas women with a body mass index between 18.5 and 25 kg/m and a waist circumference <77 cm had the highest (54% [42-66%]). The results were similar using different waist circumference cut-off values. CONCLUSION:Waist circumference was inversely related to the probability of live birth among women undergoing assisted reproductive technology independently of body mass index. 10.1016/j.ajog.2019.02.013
    The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. 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 Human reproduction update 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 and lifestyle therapy has failed. Carefully conducted and monitored pharmacological ovulation induction can achieve good cumulative pregnancy rates and multiple pregnancy rates can be minimized with adherence to recommended protocols. CC should be first-line pharmacotherapy for ovulation induction and letrozole can also be used as first-line therapy. Metformin alone has limited benefits in improving live birth rates. Gonadotropins and laparoscopic surgery can be used as second-line treatment. There is no clear evidence for efficacy of acupuncture or herbal mixtures in women with PCOS. For women with PCOS who fail lifestyle and ovulation induction therapy or have additional infertility factors, IVF can be used with the safer gonadotropin releasing hormone (GnRH) antagonist protocol. If a GnRH-agonist protocol is used, metformin as an adjunct may reduce the risk of ovarian hyperstimulation syndrome. Patients should be informed of the potential side effects of ovulation induction agents and of IVF on the foetus, and of the risks of multiple pregnancy. Increased risks for the mother during pregnancy and for the child, including the exacerbating impact of obesity on adverse outcomes, should also be discussed. 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. 10.1093/humupd/dmw025
    Effect of Preconception Impaired Glucose Tolerance on Pregnancy Outcomes in Women With Polycystic Ovary Syndrome. Wei Daimin,Zhang Bo,Shi Yuhua,Zhang Lin,Zhao Shigang,Du Yanzhi,Xu Lizhen,Legro Richard S,Zhang Heping,Chen Zi-Jiang The Journal of clinical endocrinology and metabolism 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. 10.1210/jc.2017-01294
    Repeated implantation failure versus repeated implantation success: discrimination at a metabolomic level. RoyChoudhury Sourav,Singh Apoorva,Gupta Nalini J,Srivastava Sudha,Joshi Mamata V,Chakravarty Baidyanath,Chaudhury Koel Human reproduction (Oxford, England) STUDY QUESTION:Is there any difference at the serum metabolic level between women with recurrent implantation failure (RIF) and women with recurrent implantation success (RIS) when undergoing in vitro fertilization (IVF)? SUMMARY ANSWER:Eight metabolites, including valine, adipic acid, l-lysine, creatine, ornithine, glycerol, d-glucose and urea, were found to be significantly up-regulated in women with RIF when compared with women with RIS. WHAT IS KNOWN ALREADY:Despite transfer of three high-grade embryos per cycle, RIF following three or more consecutive IVF attempts occurs in a group of infertile women. Conversely, there is a group of women who undergo successful implantation each cycle, yet have a poor obstetric history. STUDY DESIGN, SIZE, DURATION:This study was conducted over a period of 10 years (January 2004-October 2014). Groups of 28 women with RIF (age ≤40 years and BMI ≤28) and 24 women with RIS (age and BMI matched) were selected from couples with primary infertility reporting at the Institute of Reproductive Medicine, Kolkata, India. Women recruited in the RIF group had history of implantation failure in at least three consecutive IVF attempts, in which three embryos of high-grade quality were transferred in each cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS:Blood samples were collected from both the groups during the implantation window following overnight fasting for at least 10 h (7-10 days post ovulation). Samples were analyzed using a 700 MHz NMR spectrometer and acquired spectra were subjected to chemometric and statistical analysis. Serum levels of endothelial nitric oxide synthase (eNOS) were measured using an enzyme immunoassay technique. MAIN RESULTS AND THE ROLE OF CHANCE:Valine, adipic acid, l-lysine, creatine, ornithine, glycerol, d-glucose and urea were found to be significantly down-regulated in women with RIS when compared with those with RIF, with fold change values of 0.81, 0.82, 0.79, 0.80, 0.78, 0.68, 0.76 and 0.74, respectively. Further, serum eNOS was found to be significantly lower in women with RIF when compared with RIS (P < 0.05), indicating possible impairment in nitric oxide production. Metabolites, mostly related to energy metabolism, lipid metabolism and the arginine metabolic pathway were found to be considerably altered and are likely to be associated with the RIF phenomenon. However, the interplay between these molecules in RIF is complex and holds merit for further exploration. LIMITATIONS, REASONS FOR CAUTION:In-depth studies of the arginine metabolic pathway in endometrial tissues seem necessary to validate our findings. A limitation of the present study is that the metabolic level changes, eNOS and nitric oxide levels have not been investigated in the endometrial tissues of the two groups of women. It would be interesting to investigate whether there exists a direct link between metabolic dysregulation and genetic factors that affects implantation in RIF women. WIDER IMPLICATIONS OF THE FINDINGS:We speculate that tissue metabolomics can provide an improved understanding of the metabolic dysfunction associated with RIF. The identification of serum metabolic marker(s) in women with RIS may help with strategies of early therapeutic intervention, which may improve the chances of implantation significantly in women otherwise susceptible to IVF failure. STUDY FUNDING/COMPETING INTERESTS:One of the authors, S.R.C. acknowledges the Council of Scientific and Industrial Research (CSIR), Government of India [No: 9/81(1228)/14, EMR-I] for financial support. 10.1093/humrep/dew064
    Effects of polycystic ovarian syndrome on in vitro fertilization-embryo transfer outcomes are influenced by body mass index. McCormick Betsy,Thomas Michael,Maxwell Rose,Williams Daniel,Aubuchon Mira Fertility and sterility OBJECTIVE:To determine whether polycystic ovary syndrome (PCOS) adversely impacts IVF-embryo transfer outcomes in obese compared to lean patients. DESIGN:Retrospective chart review. SETTING:University-affiliated infertility program. PATIENT(S):Lean non-PCOS (n = 52), lean PCOS (n = 6), obese non-PCOS (n = 18), and obese PCOS (n = 10). INTERVENTION(S):Ninety-four fresh nondonor IVF-embryo transfer cycles analyzed. MAIN OUTCOME MEASURE(S):Cycle characteristics, clinical pregnancy (PR) and live birth rates. RESULT(S):Lean PCOS had more dominant follicles (12.2 +/- 6.0 vs. 7.7 +/- 3.6), retrieved oocytes (22.2 +/- 9.2 vs. 12.6 +/- 5.8), and frozen embryos (5 +/- 4.6 vs. 1.4 +/- 2.6) than lean non-PCOS. Lean PCOS also used fewer gonadotropin ampules (18.8 +/- 6.0 vs. 29.2 +/- 14.2), but had more retrieved oocytes (22.2 +/- 9.2 vs.14.3 +/- 4.9) than obese PCOS. Obese non-PCOS had better-grade embryos (2.1 +/- 0.8 vs. 2.7 +/- 0.8) and fewer embryos transferred (2.4 +/- 0.6 vs. 2.9 +/- 0.6) than obese PCOS, but more embryos frozen than lean non-PCOS (3.2 +/- 3.2 vs. 1.4 +/- 2.6). Implantation rates trended downward in obese patients with PCOS, but no other differences were observed. CONCLUSION(S):Patients with PCOS with a body mass index (BMI) in the lean rather than the obese range have more favorable assisted reproductive technology (ART) cycle characteristics but show no clinical outcome differences. 10.1016/j.fertnstert.2007.10.077
    Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome. Jungheim Emily S,Lanzendorf Susan E,Odem Randall R,Moley Kelle H,Chang Aimee S,Ratts Valerie S Fertility and sterility OBJECTIVE:To determine whether morbid obesity is associated with decreased pregnancy and live birth rates after IVF in women with polycystic ovary syndrome (PCOS). DESIGN:Retrospective cohort study. SETTING:University-based fertility center. PATIENT(S):Seventy-two women with PCOS who completed their first IVF cycle between 2001 and 2006. INTERVENTION(S):Outcomes of IVF were compared between women with a body mass index (BMI) of <40 kg/m(2) vs. those with a BMI of > or =40 kg/m(2). MAIN OUTCOME MEASURE(S):Clinical pregnancy rate, live birth rate. RESULT(S):Morbidly obese women with PCOS (n = 19) had significantly lower clinical pregnancy rates after IVF than patients with PCOS who were not morbidly obese (n = 53) (32% vs. 72%, relative risk 0.44, 95% confidence interval 0.22-0.87). Their live birth rates were lower too, although this difference was not statistically significant (32% vs. 60%, relative risk 0.52, 95% confidence interval 0.26-1.05). CONCLUSION(S):Morbid obesity is associated with lower pregnancy rates in women with PCOS after IVF, raising the question of whether weight loss may improve IVF success rates for morbidly obese PCOS patients. 10.1016/j.fertnstert.2008.04.063
    Effect of maternal height and weight on risk of preterm birth in singleton and twin births resulting from in vitro fertilization: a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Dickey Richard P,Xiong Xu,Gee Rebekah E,Pridjian Gabriella Fertility and sterility OBJECTIVE:To examine the effect of height, weight, and body mass index (BMI) on the risk of preterm birth of singleton and twin pregnancies conceived by vitro fertilization (IVF). DESIGN:Retrospective cohort study using 2006-2008 data from the Society for Reproductive Technology Clinic Outcome Reporting System (SART CORS). SETTING:SART-associated assisted reproductive technology programs. PATIENT(S):56,556 singleton and 23,804 twin live births resulting from fresh nondonor IVF cycles. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Rates of very early preterm (VEPTB; <28 weeks), very preterm (VPTB; <32 weeks), and preterm birth (<37 weeks) births. RESULT(S):In both singleton and twin births, increased maternal height was associated with a decreased risk of preterm birth. Maternal overweight and obesity were associated with significantly increased risk of VEPTB and VPTB in twin pregnancies. For very obese women (BMI > 35 kg/m(2)) twins were associated with a threefold increased risk of VEPTB (6.1% vs. 2.0%) and a twofold increased risk of VPTB (11.5% vs. 5.9%) compared with women of normal weight (BMI 18.4-24.9 kg/m(2)). CONCLUSION(S):Obesity and short stature significantly increase the risk of VEPTB and VPTB in twins conceived by IVF. 10.1016/j.fertnstert.2011.11.017
    Female obesity impairs in vitro fertilization outcome without affecting embryo quality. Bellver José,Ayllón Yanira,Ferrando Marcos,Melo Marco,Goyri Eduardo,Pellicer Antonio,Remohí José,Meseguer Marcos Fertility and sterility OBJECTIVE:To compare embryo quality and reproductive outcome in our IVF program according to the women's body mass index (BMI). DESIGN:Retrospective study. SETTING:University-affiliated infertility clinic, between January 2001 and April 2007. PATIENT(S):Women undergoing a total of 6,500 IVF-intracytoplasmic sperm injection (ICSI) cycles. INTERVENTION(S):Six thousand five hundred IVF-ICSI cycles were included and divided into four groups: lean (<20 kg/m(2); n = 1,070; 16.5%); normal (20-24.9 kg/m(2); n = 3,930; 60.5%); overweight (25-29.9 kg/m(2); n = 1,081; 16.6%); and obese (> or =30 kg/m(2); n = 419; 6.4%). MAIN OUTCOME MEASURE(S):Comparison of embryo quality and reproductive outcome (implantation, pregnancy, miscarriage, and live birth rates) among BMI groups. RESULT(S):No difference in insemination procedure, fertilization rate, day of ET, mean number of transferred and cryopreserved embryos, percentage of blastocyst transfers, or embryo quality on day 2 and 3 was found among groups. However, implantation, pregnancy, and live birth rates were poorer in obese women. In fact, pregnancy and live birth rates were reduced progressively with each unit of BMI (kilograms per square meter) with a significant odds ratio of 0.984 (95% confidence interval 0.972-0.997) and 0.981 (95% confidence interval 0.967-0.995), respectively. In addition, the cumulative pregnancy rate after four IVF cycles was reduced as BMI increased. CONCLUSION(S):Female obesity impairs IVF outcome, but embryo quality is not affected, pointing to an alteration in the uterine environment. 10.1016/j.fertnstert.2008.12.032
    Serum and follicular fluid monocyte chemotactic protein-1 levels are elevated in obese women and are associated with poorer clinical pregnancy rate after in vitro fertilization: a pilot study. Buyuk Erkan,Asemota Obehi A,Merhi Zaher,Charron Maureen J,Berger Dara S,Zapantis Athena,Jindal Sangita K Fertility and sterility OBJECTIVE:To determine whether monocyte chemotactic protein-1 (MCP-1), a proinflammatory chemokine important in ovulation, is abnormally elevated in obese women undergoing IVF and whether serum and follicular fluid (FF) levels of MCP-1 are associated with IVF outcome. DESIGN:Prospective pilot study. SETTING:Academic center. PATIENT(S):Women undergoing IVF. INTERVENTION(S):Serum and FF were collected from women undergoing IVF. MAIN OUTCOME MEASURE(S):Correlation between MCP-1 and other inflammatory markers with adiposity and pregnancy outcome after IVF. RESULT(S):Obese women had significantly higher serum and FF MCP-1 levels compared with overweight and normal weight women. Serum MCP-1, granulocyte colony stimulating factor, catalase, and C-reactive protein (CRP) were positively correlated with body mass index (BMI). After adjusting for age and baseline FSH, these correlations remained significant for serum MCP-1, granulocyte colony stimulating factor, and CRP. In the FF, only MCP-1 was positively correlated with BMI. Women who became pregnant had significantly lower serum MCP-1 and CRP levels compared with those who did not become pregnant; this difference was more pronounced among women with diminished ovarian reserve. Receiver operating characteristic curve demonstrated that serum MCP-1 levels >373.0 pg/mL in all women and >362.6pg/mL in women with diminished ovarian reserve predicted failure to achieve a clinical pregnancy. CONCLUSION(S):Elevations in serum and FF MCP-1 levels are positively correlated with adiposity and negatively correlated with pregnancy rates (PRs) in women undergoing IVF. 10.1016/j.fertnstert.2016.12.023
    Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008-2010 Society for Assisted Reproductive Technology registry. Provost Meredith P,Acharya Kelly S,Acharya Chaitanya R,Yeh Jason S,Steward Ryan G,Eaton Jennifer L,Goldfarb James M,Muasher Suheil J Fertility and sterility OBJECTIVE:To examine the effect of body mass index (BMI) on IVF outcomes in fresh autologous cycles. DESIGN:Retrospective cohort study. SETTING:Not applicable. PATIENT(S):A total of 239,127 fresh IVF cycles from the 2008-2010 Society for Assisted Reproductive Technology registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal BMI (18.5-24.9 kg/m(2)) were used as the reference group (REF). Subanalyses were performed on cycles reporting purely polycystic ovary syndrome (PCOS)-related infertility and those with purely male-factor infertility (34,137 and 89,354 cycles, respectively). INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Implantation rate, clinical pregnancy rate, pregnancy loss rate, and live birth rate. RESULT(S):Success rates and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for all pregnancy outcomes were most favorable in cohorts with low and normal BMIs and progressively worsened as BMI increased. Obesity also had a negative impact on IVF outcomes in cycles performed for PCOS and male-factor infertility, although it did not always reach statistical significance. CONCLUSION(S):Success rates in fresh autologous cycles, including those done for specifically PCOS or male-factor infertility, are highest in those with low and normal BMIs. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMIs. More research is needed to determine the causes and extent of the influence of BMI on IVF success rates in other patient populations. 10.1016/j.fertnstert.2015.11.008
    Extremities of body mass index and their association with pregnancy outcomes in women undergoing in vitro fertilization in the United States. Kawwass Jennifer F,Kulkarni Aniket D,Hipp Heather S,Crawford Sara,Kissin Dmitry M,Jamieson Denise J Fertility and sterility OBJECTIVE:To investigate the associations among underweight body mass index (BMI), pregnancy, and obstetric outcomes among women using assisted reproductive technology (ART). DESIGN:Retrospective cohort study using national data and log binomial regression. SETTING:Not applicable. PATIENT(S):Women undergoing IVF in the United States from 2008 to 2013. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Pregnancy outcomes (intrauterine pregnancy, live birth rates) per transfer, miscarriage rate per pregnancy, and low birth weight and preterm delivery rates among singleton and twin pregnancies. RESULT(S):For all fresh autologous in vitro fertilization (IVF) cycles in the United States from 2008 to 2013 (n = 494,097 cycles, n = 402,742 transfers, n = 180,855 pregnancies) reported to the national ART Surveillance System, compared with normal weight women, underweight women had a statistically significant decreased chance of intrauterine pregnancy (adjusted risk ratio [aRR] 0.97; 95% confidence interval [CI], 0.96-0.99) and live birth (aRR 0.95; 95% CI, 0.93-0.98) per transfer. Obese women also had a statistically decreased likelihood of both (aRR 0.94; 95% CI, 0.94-0.95; aRR 0.87; 95% CI, 0.86-0.88, respectively). Among cycles resulting in singleton pregnancy, both underweight and obese statuses were associated with increased risk of low birth weight (aRR 1.39; 95% CI, 1.25-1.54, aRR 1.26; 95% CI, 1.20-1.33, respectively) and preterm delivery (aRR 1.12; 95% CI, 1.01-1.23, aRR 1.42; 95% CI, 1.36-1.48, respectively). The association between underweight status and miscarriage was not statistically significant (aRR 1.04; 95% CI, 0.98-1.11). In contrast, obesity was associated with a statistically significantly increased miscarriage risk (aRR 1.23; 95% CI, 1.20-1.26). CONCLUSION(S):Among women undergoing IVF, prepregnancy BMI affects pregnancy and obstetric outcomes. Underweight status may have a limited impact on pregnancy and live-birth rates, but it is associated with increased preterm and low-birth-weight delivery risk. Obesity negatively impacts all ART and obstetric outcomes investigated. 10.1016/j.fertnstert.2016.08.028
    Effect of body mass index on in vitro fertilization outcomes in women with polycystic ovary syndrome. Bailey Amelia P,Hawkins Leah K,Missmer Stacey A,Correia Katharine F,Yanushpolsky Elena H American journal of obstetrics and gynecology OBJECTIVE:The objective of the investigation was to study the effect of body mass index (BMI) on in vitro fertilization (IVF) outcomes within a polycystic ovary syndrome (PCOS) population. STUDY DESIGN:This was a retrospective cohort study including 101 cycles from 79 women younger than 40 years old with a clinically documented diagnosis of PCOS by Rotterdam criteria undergoing IVF at a university-based infertility clinic from 2001 through 2010. All participants were stratified by BMI calculated from height and weight recorded within 3 months of cycle start: lean (18.7-24.9 kg/m(2), n = 51), overweight (25-29.9 kg/m(2), n = 19), and obese (≥30 kg/m(2), n = 31). Linear, logistic, and Poisson regressions were used as appropriate to estimate the effect of a range of BMIs on IVF outcomes while adjusting for potential confounders. RESULTS:Obese PCOS women had 69% lower odds of clinical pregnancy per cycle start (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11-0.86; P = .02) and 77% lower odds of clinical pregnancy per embryo transfer (OR, 0.23; 95% CI, -0.08 to 0.68; P = .008) compared with lean PCOS women. Among obese PCOS women, the odds of live birth were 71% lower per cycle start (OR, 0.29; 95% CI, 0.10-0.84; P = .02) and 77% lower per embryo transfer (OR, 0.23; 95% CI, 0.07-0.71; P = .01) compared with lean PCOS women. There was a trend toward decreased ovarian hyperstimulation syndrome incidence with increasing BMI among women with PCOS: 19.6% in lean, 10.5% in overweight, and 3.2% in obese. CONCLUSION:PCOS is a broad syndrome, with our results demonstrating 2 distinct populations, lean and obese, which have different IVF outcomes including ovarian hyperstimulation syndrome risk profiles. This information is important for clinicians because it informs treatment decisions. 10.1016/j.ajog.2014.03.035
    A Comprehensive Analysis of Body Mass Index Effect on in Vitro Fertilization Outcomes. Sarais Veronica,Pagliardini Luca,Rebonato Giorgia,Papaleo Enrico,Candiani Massimo,Viganò Paola Nutrients The effect of a raised body mass index (BMI) on the outcome of assisted reproduction technology (ART) still represents a controversial issue. Even less clear is whether BMI acts with a potential detrimental effect on IVF outcomes via a deleterious effect on innate quality of oocytes or on the environmental milieu within the uterus. With the aim to better understand the mechanisms underlying the potential deleterious effect of an increased BMI on IVF outcomes, we have evaluated the effects of female BMI on number and quality of retrieved oocytes, fertilization rate, embryo score and incidences of ongoing pregnancy and live births among couples undergoing IVF in an Italian population. Data from 1602 women who underwent their first IVF cycle were retrospectively analyzed. A significantly reduced percentage of mature oocytes when comparing obese (BMI ≥ 30 kg/m²) and normal-weight patients (BMI = 18.50-24.99 kg/m²) was found. After adjusting for maternal age and other confounders, odds for ongoing pregnancy rate showed no differences across different BMI categories. However, a significant increased odds ratio (OR) could be observed for miscarriage rate in patients with BMI ≥ 25 (OR = 2.5; p = 0.04). These results should be taken into account in order to define optimal strategies for overweight and obese patients referring to ART procedures. 10.3390/nu8030109
    Low body mass index compromises live birth rate in fresh transfer in vitro fertilization cycles: a retrospective study in a Chinese population. Cai Jiali,Liu Lanlan,Zhang Junwen,Qiu Huiling,Jiang Xiaoming,Li Ping,Sha Aiguo,Ren Jianzhi Fertility and sterility OBJECTIVE:To evaluate the effects of low body mass index (BMI) on in vitro fertilization (IVF) outcomes in fresh transfer cycles. DESIGN:Retrospective cohort study. SETTING:University-affiliated hospital. PATIENT(S):A total of 4,798 cycles with conventional stimulation and fresh transfer in a single IVF center during the period 2013-2014. Low BMI (<18.5 kg/m) was defined according to World Health Organization guidelines, and cycles within a normal weight range (18.5-24.9 kg/m) were used as reference. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Live birth rate per fresh embryo transfer. RESULT(S):Low BMI was associated with reduced live birth rates and increased miscarriage rates compared with normal weight, controlling for important covariates known to influence IVF outcomes. Patient age was the most potent confounder, causing a 10.5% reduction in the odds ratio (OR) for live birth between the groups compared. When an interaction term (age × BMI) was introduced, the OR for live birth was reduced in cycles of those aged ≥35 years compared with cycles of those aged 28-34 years, whereas the change in OR between cycles in those aged <28 and cycles in those aged 28-34 years was insignificant. CONCLUSION(S):Low BMI is associated with negative outcomes in fresh transfer cycles, especially for women of advanced age. 10.1016/j.fertnstert.2016.10.029
    Anti-Inflammatory Dietary Combo in Overweight and Obese Women with Polycystic Ovary Syndrome. Salama Amany Alsayed,Amine Ezzat Khamis,Salem Hesham Abd Elfattah,Abd El Fattah Nesrin Kamal North American journal of medical sciences BACKGROUND:Polycystic ovary syndrome (PCOS) is of clinical and public health importance, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive, metabolic, and psychological features. AIM:The study was to investigate the effect of anti-inflammatory dietary combo on metabolic, endocrine, inflammatory, and reproductive profiles in overweight and obese women with PCOS. MATERIALS AND METHODS:A total of 100 nonpregnant, overweight, and obese adult females with PCOS according to the Rotterdam criteria, were screened during the year 2012, and 75 completed the trial. At baseline and study end, fasting blood samples were drawn to measure biological markers, body fat percent (BFP), and visceral fat area (VFA) were assessed by the InBody720 device and anthropometric measurements were done for all participants who were subjected to an anti-inflammatory hypocaloric diet and physical activity for 12 weeks. RESULTS:At study completion, we achieved moderate weight loss of (± 7%) and significant improvements in body composition, hormones and menstrual cyclicity, blood pressure, glucose homeostasis, dyslipidemia, C-reactive protein (CRP), and serum amyloid A (SAA) (surrogate measures of cardiovascular risk (CVR)). This was a clinically relevant weight loss that is associated with a reduced prevalence of type 2 diabetes mellitus (DM2) and metabolic syndrome (MS) in the general population and improved fertility outcomes in PCOS. We achieved 63% regain of menstrual cyclicity and 12% spontaneous pregnancy rate within 12 week. CONCLUSIONS:We have explored an additional dietary treatment option with good prognostic metabolic and reproductive responses to weight loss that occur in overweight and obese PCOS. 10.4103/1947-2714.161246
    Lifestyle intervention up-regulates gene and protein levels of molecules involved in insulin signaling in the endometrium of overweight/obese women with polycystic ovary syndrome. Ujvari D,Hulchiy M,Calaby A,Nybacka Å,Byström B,Hirschberg A L Human reproduction (Oxford, England) STUDY QUESTION:Does lifestyle intervention aiming at weight loss influence endometrial insulin signaling in overweight/obese women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER:Lifestyle intervention up-regulates, both at the mRNA and protein levels, components of insulin signaling in the endometrium of overweight/obese PCOS women, in relation to an improved menstrual pattern. WHAT IS KNOWN ALREADY:PCOS is a multifactorial endocrine disorder diagnosed by two of the following three criteria: chronic anovulation, hyperandrogenism and polycystic ovaries. Many women with PCOS also have insulin resistance and obesity. The syndrome is furthermore associated with endometrial cancer and possible alterations in endometrial function and receptivity. STUDY DESIGN, SIZE, DURATION:This study assessed the effects of a combined diet and exercise lifestyle intervention for 3 months. PARTICIPANTS/MATERIALS, SETTING, METHODS:A group of 20 overweight/obese PCOS women with anovulation, hyperandrogenism and polycystic ovaries were subjected to a combined diet and exercise program for 3 months. Ten body mass index (BMI)-matched regularly menstruating overweight/obese controls, nine normal-weight PCOS women and ten normal-weight controls were also included in the study. In an academic clinical setting, women were examined in mid-follicular phase for endocrine assessment and determination of endometrial levels of mRNA and immunohistochemical staining of insulin signaling molecules (the insulin receptor, insulin receptor substrate-1 (IRS1) and glucose transporter (GLUT) 1 and 4). MAIN RESULTS AND THE ROLE OF CHANCE:Women with PCOS exhibited lower levels of IRS1 (P < 0.01) and GLUT4 (P < 0.01) mRNA in their proliferative endometrium than BMI-matched controls. After lifestyle intervention, weight loss averaged 4.7% and the menstrual pattern improved in 65% of the overweight/obese women with PCOS. Levels of IRS1 (P < 0.01) and GLUT1 (P < 0.05) mRNA were significantly up-regulated in the endometrium of those women with improved menstrual function, as were the protein expression levels of pY612IRS1 (the activated IRS1 form, P < 0.05), pS312IRS1 (the inhibitory form of IRS1, P < 0.05) and GLUT1 (P < 0.05). Improvement in the menstrual function of women in the obese/overweight group following the lifestyle intervention was positively correlated with the increase in the endometrial level of IRS1 mRNA (r = 0.63, P < 0.01) and negatively correlated with the change in BMI (r = -0.50, P < 0.05). LIMITATIONS, REASONS FOR CAUTION:The number of women in each group was limited, although the power calculation indicated that the number of patients subjected to the lifestyle intervention was sufficient. WIDER IMPLICATIONS OF THE FINDINGS:We propose that up-regulation of endometrial IRS1 and GLUT1 in overweight/obese women with PCOS following lifestyle intervention improves the glucose homeostasis and thereby restores the functioning of the endometrium in these women. STUDY FUNDING/COMPETING INTEREST(S):This study was supported financially by the Swedish Research Council (A.L.H., 20324), Karolinska Institutet and the Stockholm County Council. None of the authors has any conflict of interest to declare. 10.1093/humrep/deu114
    Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome. Legro Richard S,Dodson William C,Kris-Etherton Penny M,Kunselman Allen R,Stetter Christy M,Williams Nancy I,Gnatuk Carol L,Estes Stephanie J,Fleming Jennifer,Allison Kelly C,Sarwer David B,Coutifaris Christos,Dokras Anuja The Journal of clinical endocrinology and metabolism CONTEXT:Lifestyle modification is recommended in women with polycystic ovary syndrome (PCOS) prior to conception but there are few randomized trials to support its implementation or benefit. OBJECTIVE:This study aimed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS. DESIGN, SETTING, AND PARTICIPANTS:This was a randomized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS, age 18-40 y and body mass index 27-42 kg/m(2). INTERVENTION:Women were randomly assigned to receive either 16 weeks of 1) continuous oral contraceptive pills (OCPs) (ethinyl estradiol 20 mcg/1 mg norethindrone acetate) ("OCP"); 2) lifestyle modification consisting of caloric restriction with meal replacements, weight loss medication (either sibutramine, or orlistat), and increased physical activity to promote a 7% weight loss ("Lifestyle"); or 3) combined treatment with both OCP and lifestyle modification ("Combined"). After preconception intervention, women underwent standardized ovulation induction with clomiphene citrate and timed intercourse for four cycles. Pregnancies were followed with trimester visits until delivery. MAIN OUTCOME MEASURES:Weight, ovulation, and live birth were measured. RESULTS:We consented 216 and randomly assigned 149 women (Lifestyle: n = 50; OCP: n = 49; Combined: n = 50). We achieved significant weight loss with both Lifestyle (mean weight loss, -6.2%; 95% confidence interval (CI), -7.4--5.0; and Combined (mean weight loss, -6.4%; 95% CI, -7.6--5.2) compared with baseline and OCP (both P < .001). There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP (odds ratio [OR, 2.47; 95% CI, 1.42-4.27) whereas no change in metabolic syndrome was detected in the Lifestyle (OR, 1.18; 95% CI, 0.63-2.19) or Combined (OR, 0.72; 95% CI, 0.44-1.17) groups. Cumulative ovulation rates were superior after weight loss: OCP, 46%; Lifestyle, 60%; and Combined, 67% (P < .05). Live birth rates were OCP, 12%; Lifestyle, 26%; and Combined, 24% (P = .13). CONCLUSIONS:A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and, compared with oral contraceptive pretreatment, leads to higher ovulation rates. 10.1210/jc.2015-2778
    Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS. Legro Richard S,Dodson William C,Kunselman Allen R,Stetter Christy M,Kris-Etherton Penny M,Williams Nancy I,Gnatuk Carol L,Estes Stephanie J,Allison Kelly C,Sarwer David B,Diamond Michael P,Schlaff William D,Casson Peter R,Christman Gregory M,Barnhart Kurt T,Bates G Wright,Usadi Rebecca,Lucidi Scott,Baker Valerie,Zhang Heping,Eisenberg Esther,Coutifaris Christos,Dokras Anuja The Journal of clinical endocrinology and metabolism CONTEXT:In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown. OBJECTIVE:We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS. DESIGN, SETTING, AND PARTICIPANTS:This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18-40 years of age who were overweight/obese and infertile with PCOS. INTERVENTION:We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142). MAIN OUTCOME MEASURES:Live birth, pregnancy loss, and ovulation were measured. RESULTS:In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1-1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2-1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.7; P = .01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.8; P = .01). CONCLUSIONS:These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment. 10.1210/jc.2016-1659
    Lifestyle modification programs in polycystic ovary syndrome: systematic review and meta-analysis. Domecq Juan Pablo,Prutsky Gabriela,Mullan Rebecca J,Hazem Ahmad,Sundaresh Vishnu,Elamin Mohammed B,Phung Olivia J,Wang Amy,Hoeger Kathleen,Pasquali Renato,Erwin Patricia,Bodde Amy,Montori Victor M,Murad M Hassan The Journal of clinical endocrinology and metabolism CONTEXT:Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. OBJECTIVE:The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. DATA SOURCES:Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). STUDY SELECTION:We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. DATA EXTRACTION:Two authors performed the data extraction independently. DATA SYNTHESIS:We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, -2.3 mg/dL; 95% confidence interval, -4.5 to -0.1, I² = 72%, P = .04) and fasting blood insulin (weighted mean difference, -2.1 μU/mL, 95% confidence interval, -3.3 to -1.0, I² = 0%, P < .001). Changes in body mass index were associated with changes in fasting blood glucose (P < .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. CONCLUSIONS:The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain. 10.1210/jc.2013-2385
    [Randomized trial of a lifestyle program in obese infertile women]. Mutsaerts M A Q Nederlands tijdschrift voor geneeskunde OBJECTIVE:Small intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcome, but large randomized controlled trials (RCT) are lacking. Our objective was to investigate the effects of a lifestyle intervention in obese infertile women in a multicenter RCT. DESIGN:We randomly assigned infertile women with body mass index ≥ 29 k/m² to a six-month lifestyle intervention preceding infertility treatment or to prompt infertility treatment. The primary outcome was the vaginal birth of a healthy singleton at term within 2 years of randomization. RESULTS:Between June 2009-June 2102 we randomly allocated 577 women to one of two treatment strategies: 290 to lifestyle intervention preceding infertility treatment (intervention group) and 287 to prompt infertility treatment (control group). Three women withdrew informed consent, leaving 289 and 285 women for analysis. Discontinuation rate during the lifestyle intervention was 22%. Mean weight loss in the intervention group was 4.4 kg and in the control group 1.1 kg ( p < 0.001); the primary outcome occurred in 76 women (27%) in the intervention group versus 100 (35%) in the control group (RR: 0.77, 95% CI 0.60 to 0.99). The number of natural conceptions leading to ongoing pregnancies was 73 (26%) versus 46 (16%) (RR: 1.6, 95% CI 1.2 to 2.2). Maternal pregnancy-related and labor-related complications and neonatal complications were comparable. CONCLUSION:In obese infertile women lifestyle intervention preceding infertility treatment did not result in better rates of vaginal birth of healthy singletons at term as compared to prompt infertility treatment.
    Randomized Trial of a Lifestyle Program in Obese Infertile Women. Mutsaerts Meike A Q,van Oers Anne M,Groen Henk,Burggraaff Jan M,Kuchenbecker Walter K H,Perquin Denise A M,Koks Carolien A M,van Golde Ron,Kaaijk Eugenie M,Schierbeek Jaap M,Oosterhuis Gerrit J E,Broekmans Frank J,Bemelmans Wanda J E,Lambalk Cornelis B,Verberg Marieke F G,van der Veen Fulco,Klijn Nicole F,Mercelina Patricia E A M,van Kasteren Yvonne M,Nap Annemiek W,Brinkhuis Egbert A,Vogel Niels E A,Mulder Robert J A B,Gondrie Ed T C M,de Bruin Jan P,Sikkema J Marko,de Greef Mathieu H G,ter Bogt Nancy C W,Land Jolande A,Mol Ben W J,Hoek Annemieke The New England journal of medicine BACKGROUND:Small lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking. METHODS:We randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization. RESULTS:We assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in the analysis. The discontinuation rate in the intervention group was 21.8%. In intention-to-treat analyses, the mean weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group (P<0.001). The primary outcome occurred in 27.1% of the women in the intervention group and 35.2% of those in the control group (rate ratio in the intervention group, 0.77; 95% confidence interval, 0.60 to 0.99). CONCLUSIONS:In obese infertile women, a lifestyle intervention preceding infertility treatment, as compared with prompt infertility treatment, did not result in higher rates of a vaginal birth of a healthy singleton at term within 24 months after randomization. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1530.). 10.1056/NEJMoa1505297
    Effectiveness of lifestyle intervention in subgroups of obese infertile women: a subgroup analysis of a RCT. van Oers A M,Groen H,Mutsaerts M A Q,Burggraaff J M,Kuchenbecker W K H,Perquin D A M,Koks C A M,van Golde R,Kaaijk E M,Schierbeek J M,Oosterhuis G J E,Broekmans F J,Vogel N E A,Land J A,Mol B W J,Hoek A, Human reproduction (Oxford, England) STUDY QUESTION:Do age, ovulatory status, severity of obesity and body fat distribution affect the effectiveness of lifestyle intervention in obese infertile women? SUMMARY ANSWER:We did not identify a subgroup in which lifestyle intervention increased the healthy live birth rate however it did increase the natural conception rate in anovulatory obese infertile women. WHAT IS KNOWN ALREADY:Obese women are at increased risk of infertility and are less likely to conceive after infertility treatment. We previously demonstrated that a 6-month lifestyle intervention preceding infertility treatment did not increase the rate of healthy live births (vaginal live birth of a healthy singleton at term) within 24 months of follow-up as compared to prompt infertility treatment in obese infertile women. Natural conceptions occurred more frequently in women who received a 6-month lifestyle intervention preceding infertility treatment. STUDY DESIGN, SIZE, DURATION:This is a secondary analysis of a multicentre RCT (randomized controlled trial), the LIFEstyle study. Between 2009 and 2012, 577 obese infertile women were randomly assigned to a 6-month lifestyle intervention followed by infertility treatment (intervention group) or to prompt infertility treatment (control group). Subgroups were predefined in the study protocol, based on frequently used cut-off values in the literature: age (≥36 or <36 years), ovulatory status (anovulatory or ovulatory), BMI (≥35 or <35 kg/m) and waist-hip (WH) ratio (≥0.8 or <0.8). PARTICIPANTS/MATERIALS, SETTING, METHODS:Data of 564 (98%) randomized women who completed follow-up were analyzed. We studied the effect of the intervention program in various subgroups on healthy live birth rate within 24 months, as well as the rate of overall live births (live births independent of gestational age, mode of delivery and health) and natural conceptions within 24 months. Live birth rates included pregnancies resulting from both treatment dependent and natural conceptions. Logistic regression models with randomization group, subgroup and the interaction between randomization group and subgroup were used. Significant interaction was defined as a P-value <0.1. MAIN RESULTS AND THE ROLE OF CHANCE:Neither maternal age, ovulatory status nor BMI had an impact on the healthy live birth rate within 24 months, nor did they influence the overall live birth rate within 24 months after randomization. WH ratio showed a significant interaction with the effect of lifestyle intervention on healthy live birth rate (P = 0.05), resulting in a lower healthy live birth rate in women with a WH ratio <0.8. WH ratio had no interaction regarding overall live birth rate (P = 0.27) or natural conception rate (P = 0.38). In anovulatory women, the effect of lifestyle intervention resulted in more natural conceptions compared to ovulatory women (P-value for interaction = 0.02). There was no interaction between other subgroups and the effect of the intervention on the rate of natural conception. LIMITATIONS, REASONS FOR CAUTION:Since this was a subgroup analysis of a RCT and sample size determination of the trial was based on the primary outcome of the study, the study was not powered for analyses of all subgroups. WIDER IMPLICATIONS OF THE FINDINGS:Our finding that lifestyle intervention leads to increased natural conception in anovulatory obese women could be used in the counselling of these women, but requires further research using an appropriately powered study in order to confirm this result. STUDY FUNDING/COMPETING INTERESTS:The study was supported by a grant from ZonMw, the Dutch Organisation for Health Research and Development (50-50110-96-518). The Department of Obstetrics and Gynaecology of the UMCG received an unrestricted educational grant from Ferring pharmaceuticals BV, The Netherlands. Ben Mol is a consultant for ObsEva, Geneva. Annemieke Hoek received a speaker's fee for a postgraduate education from MSD pharmaceutical company, outside the submitted work. TRIAL REGISTRATION NUMBER:The LIFEstyle study was registered at the Dutch trial registry (NTR 1530). 10.1093/humrep/dew252
    Clinical and laboratory parameters and morphological characteristics of the endometrium in women with impaired fat metabolism and failed IVF attempts. Lisovskaya Tatiana V,Perepletina Tatiana A,Sevost' Yanova Ol'ga Y,Mayasina Elena N,Salimov Daniil F,Osipenko Anna A Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology To study clinical and laboratory parameters and morphological characteristics of the endometrium in women with impaired fat metabolism and failed IVF attempts. Clinical examination, laboratory tests, morphological analysis, and immunohistochemistry of the endometrium were conducted in 76 patients with different BMI, followed up with infertility and failed IVF attempts. Patients were divided into four groups by body mass index (BMI): 1 group - 17 women with overweight, BMI = 25.0 - 29.9 kg/m; 2 group - 15 women with class I obesity, BMI 30.0-34.9 kg/m; 3 group - 14 women with class II obesity, BMI 35.0-39.9 kg/m; and the control group of 30 women with normal weight, BMI 18.5-24.9 kg/m. Clinical and laboratory analysis revealed menstrual irregularities and hormonal imbalance such as hypoestrogenism. Immunohistochemistry of the endometrium found a significant decrease in the expression of ERα and PR receptors in the glands correlated to increasing BMI. Pregravid preparation of women with increased BMI and failed IVF attempts has to include life-style modification and weight reduction program to restore normal hormonal status and expression of estrogen and progesterone receptors, prevention of excessive proliferative processes in the endometrium, and improving endometrial receptivity. 10.1080/09513590.2019.1653561
    [Infertility: A key time to follow a medical nutritional management. Our experience on 78 patients]. Parent C,Pigeyre M,Pleuvret A,Thomas P,Deruelle P,Dewailly D,Catteau-Jonard S Gynecologie, obstetrique & fertilite OBJECTIVES:The prevalence of female obesity is increasing. Obesity leads to increased infertility and difficulties in the management of Assisted Reproductive Technology (ART). A specialized nutritional consultation was created in 2008 at University Hospital of Lille, to support infertile obese and overweight patients and to achieve a BMI below 35kg/m(2) before pregnancy. The aim of this retrospective study was to evaluate our practice of nutritional support on weight and pregnancy rate. METHODS:Seventy-eight obese or overweight patients, followed in nutrition and ART for at least two years, were compared to a control group of 119 normal weight patients. The nutritional strategy was mainly based on lifestyle changes, to establish healthier food and higher physical activity. RESULTS:The mean initial BMI was 37.5kg/m(2) vs 35.6kg/m(2) after nutritional support (significant weight loss, [P<0.001]). Obese or overweight patients had more frequently metabolic syndrome (P<0.01). The chances of pregnancy, after weight loss, were similar to the control group both in IUI and IVF/ICSI. However, gonadotropin doses were increased in the obese and overweight group (P=0.007). The hypocaloric diet was the most effective nutritional strategy to achieve a weight loss greater than 5% of initial weight (P=0.017). Regular physical activity practice allowed also more frequently to achieve this goal (P=0.074). Even after weight loss, a significant number of gestational diabetes (25% of pregnancies in our population) occurred in the obese or overweight group. CONCLUSION:This nutritional consultation promotes weight loss in infertile obese or overweight patients. The maternity desire is a strong motivational lever to weight loss, which leads to satisfying pregnancy rate. 10.1016/j.gyobfe.2016.01.006
    No effect of weight intervention on perinatal outcomes in obese women scheduled for in vitro fertilization treatment. Einarsson Snorri,Bergh Christina,Kluge Linda,Thurin-Kjellberg Ann Acta obstetricia et gynecologica Scandinavica INTRODUCTION:Large observational studies have shown that obstetric and perinatal outcomes are negatively affected in obese women. In contrast, a recent Dutch randomized trial of infertile women and lifestyle weight intervention found no difference between the weight intervention group and the control group in obstetric or neonatal outcomes. We have recently published a large Nordic randomized trial where obese women scheduled for in vitro fertilization (IVF) treatment went through an intensive weight intervention treatment before IVF. No significant effect on live birth rate was found, despite large weight loss in the intervention group. The present study was conducted primarily to find out the effect of weight intervention in obese women scheduled for IVF on mean birthweight and mean deviation from expected birthweight, and secondarily the effect on other perinatal and maternal outcomes. MATERIAL AND METHODS:A secondary analysis of a prospective, randomized controlled trial performed between 2010 and 2016 in the Nordic countries was performed. In all, 317 women were randomized either to weight reduction and IVF treatment (n = 160) or IVF only (n = 157) and the primary end-point was live birth. From this study, all births were analyzed for perinatal and maternal outcomes. Nine infertility clinics participated, including women < 38 years of age planning for IVF, and having a body mass index ≥ 30 and < 35 kg/m . Data concerning perinatal and maternal outcomes were gathered from maternal health-care and delivery records for mother and child. All analyses were performed on singletons only. RESULTS:There were 87 live births, 45 singletons in the intervention group and 41 singletons and one twin birth in the control group. The maternal characteristics for the women having a live birth were comparable in the two groups. The primary outcomes, mean birthweight, in the weight intervention and IVF group and the IVF only group were; 3486 g (standard deviation [SD] 523) vs 3584 g (SD 509) (P = 0.46), mean difference -98.6 g (95% confidence interval [CI] -320.3 to 123.2); deviation from expected birthweight 0.25% (SD 10.4) vs 0.87% (SD 12.9), mean difference 1.1% (95% CI -6.1 to 3.9). The estimates of the secondary perinatal and maternal outcomes in the 2 groups were: preterm birth < 37 weeks 2 (4.4%) vs 1 (2.4%) (odds ratio [OR] 1.95; 95% CI 0.17-22.36), small-for-gestational-age 0 (0%) vs 1 (2.4%), mean gestational age (days) 278 vs 280 (P = 0.95), preeclampsia 5 (11.1%) vs 4 (9.8%) (OR 1.19; 95% CI 0.30-4.76), cesarean section 13 (28.9%) vs 10 (24.4%) (OR 1.14; 95% CI 0.45-2.94). CONCLUSIONS:The outcomes in both groups were generally good. There are no indications that weight intervention in this setting, in infertile women with obesity WHO class 1 undergoing IVF, has a negative impact on mean birthweight and deviation from expected birthweight. However, the data are not sufficiently robust to draw firm conclusions concerning other outcomes. 10.1111/aogs.13532
    Weight loss improves reproductive outcomes in obese women undergoing fertility treatment: a randomized controlled trial. Sim K A,Dezarnaulds G M,Denyer G S,Skilton M R,Caterson I D Clinical obesity For women attempting pregnancy, obesity reduces fertility and is an independent risk factor for obstetric and neonatal complications. The aim of this evaluator-blinded, randomized controlled trial was to evaluate a weight loss intervention on pregnancy rates in obese women undertaking fertility treatment. Forty-nine obese women, aged ≤ 37 years, presenting for fertility treatment were randomized to either a 12-week intervention (n = 27) consisting of a very-low-energy diet for the initial 6 weeks followed by a hypocaloric diet, combined with a weekly group multidisciplinary programme; or a control group (n = 22) who received recommendations for weight loss and the same printed material as the intervention. Anthropometric and reproductive parameters were measured at baseline and at 12 weeks. The 22 women who completed the intervention had greater anthropometric changes (-6.6 ± 4.6 kg and -8.7 ± 5.6 cm vs. -1.6 ± 3.6 kg and -0.6 ± 6.3 cm) compared with the control group (n = 17; P < 0.001). The intervention group achieved a pregnancy rate of 48% compared with 14% (P = 0.007), took a mean two fertility treatment cycles to achieve each pregnancy compared with four in the control group (P = 0.002), and had a marked increase in the number of live births (44% vs. 14%; P = 0.02). A group weight loss programme, incorporating dietary, exercise and behavioural components, is associated with a significant improvement in pregnancy rates and live births in a group of obese women undergoing fertility treatment. 10.1111/cob.12048
    Weight decrease improves live birth rates in obese women undergoing IVF: a pilot study. Espinós Juan J,Polo Ana,Sánchez-Hernández Juan,Bordas Ramón,Pares Pere,Martínez Olga,Calaf Joaquim Reproductive biomedicine online Obese women have lower pregnancy rates than normal-weight women undergoing assisted reproductive treatment. We conducted a pilot study to evaluate whether a 12-week diet and exercise intervention before an IVF cycle would influence pregnancy rates in obese women. Forty-one patients were enrolled in this study. They were randomly allocated to two groups: an intervention group (n = 21), who underwent an individualized diet and physical exercise programme supervised by a dietician, and a control group (n = 20), who started IVF with no previous intervention. The primary outcome was clinical pregnancy rate after a single treatment cycle. Mean weight loss in the study group after the intervention was 5.4 kg (range 1.1-14.6 kg). The study and control groups had similar total FSH consumption, number of oocytes and embryos obtained, and number and quality of embryos transferred. There was a non-significant trend towards a higher clinical pregnancy rate after fresh embryo transfer (66.7% versus 41.2%). The intervention group had a significantly higher cumulative live birth rate (61.9% versus 30%, P = 0.045) (odds ratio for intervention group, 3.8; 95% confidence interval, 1.03 to 13.9) The data suggest that weight loss resulted in a significantly increased cumulative live birth rate. 10.1016/j.rbmo.2017.06.019
    Weighing the Impact of Diet and Lifestyle on Female Reproductive Function. Garruti Gabriella,Depalo Raffaella,De Angelis Maria Current medicinal chemistry BACKGROUND:In the last years, several scientific societies and expert groups focused on the role played by nutritional factors, lifestyle and excess of body fat in interfering with female reproduction and fertility. In many studies a confounding factor is represented by polycystic ovary syndrome (PCOS) which is one of the major causes of infertility where genetic and family history are certainly playing a role, together with lifestyle and nutritional factors. METHODS:In an attempt to define "the optimal fertility diet", we consider the role played by Mediterranean lifestyle and some macronutrients (animal and vegetable proteins) on ovulatory disorders and female fertility also considering some new visions derived from randomized trials of lifestyle programs in obese infertile women asking for in vitro fertilization or alternative assisted reproduction technologies. RESULTS:Several reports are in favor of an increased consumption of either proteins or low-glycemic index carbohydrates to improve ovulatory disorders and female fertility. In studies concerning infertile women undergoing assisted reproduction, either structured exercise sessions and dietary intervention programs seem to be effective in improving menstrual cycles and fertility as demonstrated by the increased rate of natural conceptions. CONCLUSION:The findings of this review confirm the important impact of Mediterranean diet and lifestyle in preserving and improving fertility. However, epigenetic factors are very important in determining fertility rate, but genetic background and ethnicity are also playing crucial roles. 10.2174/0929867324666170518101008
    Adherence to the Mediterranean diet and IVF success rate among non-obese women attempting fertility. Karayiannis Dimitrios,Kontogianni Meropi D,Mendorou Christina,Mastrominas Minas,Yiannakouris Nikos Human reproduction (Oxford, England) STUDY QUESTION:Is adherence to the Mediterranean diet (MedDiet) associated with better IVF performance in women attempting fertility? SUMMARY ANSWER:Greater adherence to the MedDiet, defined using the validated Mediterranean diet score (MedDietScore), was associated with a higher likelihood of achieving clinical pregnancy and live birth among non-obese women <35 years of age. WHAT IS KNOWN ALREADY:Diet impacts fertility and certain nutrients and food groups appear to have a greater effect on reproductive health, but there are relatively few published data on the role of dietary patterns, and the MedDiet in particular, on assisted reproductive performance. STUDY DESIGN, SIZE, DURATION:This prospective cohort study included 244 non-obese women (22-41 years of age; BMI < 30 kg/m2) who underwent a first IVF treatment in an Assisted Conception Unit in Athens, Greece, between November 2013 and September 2016. The study was designed to evaluate the influence of habitual dietary intake and lifestyle on fertility outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS:Diet was assessed before the IVF treatment via a validated food-frequency questionnaire. Adherence to the MedDiet was assessed through the MedDietScore (range: 0-55), with higher scores indicating greater adherence. Intermediate outcomes (oocyte yield, fertilization rate and embryo quality measures) and clinical endpoints (implantation, clinical pregnancy and live birth) were abstracted from electronic medical records. Associations between MedDietScore and IVF outcomes were analysed using generalized linear models adjusting for age, ovarian stimulation protocol, BMI, physical activity, anxiety levels, infertility diagnosis, caloric intake and supplements use. MAIN RESULTS AND THE ROLE OF CHANCE:No association of MedDietScore with any of the intermediate outcomes or with implantation was found. However, compared with women in the highest tertile of the MedDietScore (≥36, n = 86), women in the lowest tertile (≤30, n = 79) had significantly lower rates of clinical pregnancy (29.1 vs 50.0%, P = 0.01) and live birth (26.6 vs 48.8%, P = 0.01). The multivariable-adjusted relative risk (95% CI) for clinical pregnancy comparing women in the lowest with women in the highest tertile of the MedDietScore was 0.35 (0.16-0.78; P-trend=0.01), and for live birth it was 0.32 (0.14-0.71; P-trend = 0.01). These associations were significantly modified by women's age (P-interaction <0.01 for both outcomes). MedDietScore was positively related to clinical pregnancy and live birth among women <35 years old (P ≤ 0.01) but not among women ≥35 years. Among women <35 years, a beneficial 5-point increase in the MedDietScore was associated with ~2.7 times higher likelihood of achieving clinical pregnancy and live birth. LIMITATIONS, REASONS FOR CAUTION:Our finding cannot be generalized to the whole reproductive population nor to obese women nor to women attending infertility clinics around the world. In addition, due to the observational study design, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS:The results suggest that diet modifications and greater compliance to the Mediterranean diet may help increase the chances of a successful pregnancy and delivering a live baby for women undergoing IVF treatment. STUDY FUNDING/COMPETING INTEREST(S):This work was partially supported by a grand from Harokopio University (KE321). All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER:NCT03050944. 10.1093/humrep/dey003
    Diet and IVF pilot study: short-term weight loss improves pregnancy rates in overweight/obese women undertaking IVF. Moran Lisa,Tsagareli Victoria,Norman Robert,Noakes Manny The Australian & New Zealand journal of obstetrics & gynaecology Obesity worsens and modest weight loss improves female fertility. Overweight women were randomised to lifestyle or standard treatment pre-in vitro fertilisation with treatment cessation at embryo transfer. There was a greater reduction in weight (P < 0.001) for lifestyle treatment (-3.8 ± 3.0 kg, P < 0.001) compared with no changes for standard treatment (-0.5 ± 1.2 kg, P = 0.092). Both the intervention (-5.3 ± 4.6 cm) and control (-3.5 ± 3.5 cm) group had reductions in waist circumference (P < 0.001) with no differences between the two groups (P = 0.215). The overall pregnancy rate was 53% (20/38) for the intervention and control group combined. 10.1111/j.1479-828X.2011.01343.x
    The role of female obesity on in vitro fertilization outcomes. Kasum Miro,Orešković Slavko,Čehić Ermin,Lila Albert,Ejubović Emina,Soldo Dragan Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology The aim of this review is to analyze the role of obesity on fertility outcome in women undergoing in vitro fertilization (IVF) with respect to clinical or live birth rates and pregnancy loss rates. Despite findings from several earlier and newer studies that obesity does not adversely affect pregnancy outcome in women attempting conception, numerous reports from mostly recent studies suggest that obesity undoubtedly impairs IVF outcomes. Obesity impairs ovarian responsiveness to gonadotrophin stimulation, requiring higher doses of medication, increased risk of cycle cancelation, pre-term delivery, low birth weight or miscarriage, and decreases implantation, clinical pregnancy or live birth rates compared to women of normal weight. The mechanisms underlying the adverse effects of female obesity on IVF outcome may be primarily explained by functional alterations to the hypothalamic-pituitary-ovarian axis. Additionally, obesity appears to affect deleteriously the number and quality of oocytes or embryos, and impairs endometrial decidualization which is necessary for uterine receptivity. Nevertheless, attaining normal body weight by the use of lifestyle modifications, including a healthy diet and exercise over time of several months before and during an IVF treatment, may be successful in achievement of gradual and sustainable weight loss with improvement of IVF outcome. 10.1080/09513590.2017.1391209
    Short-term effects of a hypocaloric diet with low glycemic index and low glycemic load on body adiposity, metabolic variables, ghrelin, leptin, and pregnancy rate in overweight and obese infertile women: a randomized controlled trial. Becker Geórgia F,Passos Eduardo P,Moulin Cileide C The American journal of clinical nutrition BACKGROUND:Obesity is related to hormonal disorders that affect the reproductive system. Low-glycemic index (LGI) diets seem to exert a positive effect on weight loss and on metabolic changes that result from obesity. OBJECTIVE:We investigated the effects of a hypocaloric diet with an LGI and low glycemic load on anthropometric and metabolic variables, ghrelin and leptin concentrations, and the pregnancy rate in overweight and obese infertile women who were undergoing in vitro fertilization (IVF). DESIGN:The study was a randomized block-design controlled trial in which we analyzed 26 overweight or obese infertile women. Patients were assigned to a hypocaloric LGI-diet group or a control group and followed the protocol for 12 wk. Body weight, body mass index (BMI), percentage of body fat, glucose, insulin, homeostasis model assessment of insulin resistance, serum lipids, reproductive hormones, leptin, acylated ghrelin, number of oocytes retrieved in the IVF cycle, and pregnancy rate were determined. RESULTS:There were greater reductions in body mass, BMI, percentage of body fat, waist:hip ratio, and leptin in the LGI-diet group than in the control group (P < 0.05). Despite a change of 18% in mean values, there was no significant increase in acylated ghrelin concentrations in the LGI group compared with the control group (P = 0.215). The LGI-diet group had 85.4% more oocytes retrieved than did the control group (7.75 ± 1.44 and 4.18 ± 0.87, respectively; P = 0.039) in the IVF cycle. Three patients (21.4%) in the LGI group experienced a spontaneous pregnancy during the follow-up, which generated 3 live births. CONCLUSIONS:The hypocaloric LGI diet promoted a decrease in BMI, percentage of body fat, and leptin concentrations, which improved oocyte development and pregnancy rate. These results support the clinical recommendation to advise overweight and obese women to lose weight through a balanced diet before being submitted for treatment with assisted reproduction technologies. A hypocaloric diet combined with LGI foods seems to be beneficial for these patients, but additional studies are required before this treatment is recommended. This trial was registered at clinicaltrials.gov as NCT02416960. 10.3945/ajcn.115.117200
    Prepregnancy dietary patterns and risk of pregnancy loss. Gaskins Audrey J,Rich-Edwards Janet W,Hauser Russ,Williams Paige L,Gillman Matthew W,Penzias Alan,Missmer Stacey A,Chavarro Jorge E The American journal of clinical nutrition BACKGROUND:Two previous case-control studies observed associations between specific food groups and risk of miscarriage; however, to our knowledge, no previous studies have investigated dietary patterns and risk of pregnancy loss. OBJECTIVE:We aimed to assess prepregnancy adherence to the alternate Healthy Eating Index 2010 (aHEI-2010), alternate Mediterranean diet (aMED), and Fertility Diet (FD) and risk of pregnancy loss. DESIGN:Our prospective cohort study included 15,950 pregnancies reported by 11,072 women in the Nurses' Health Study II between 1992 and 2009. Diet was assessed every 4 y starting in 1991 by using a validated food-frequency questionnaire. Prepregnancy dietary pattern scores were computed as the sum of a woman's score on each pattern's predefined components. Multivariable log-binomial regression models with generalized estimating equations were used to estimate RRs and 95% CIs. RESULTS:Incident spontaneous abortions and stillbirths were reported in 2756 (17.3%) and 120 (0.8%) pregnancies, respectively. None of the 3 dietary patterns were associated with risk of pregnancy loss. In the multivariable model, RR of pregnancy loss for a 1-SD increase in score was 1.02 (95% CI: 0.98, 1.05) for the aMED pattern, 1.01 (95% CI: 0.98, 1.05) for the aHEI-2010 pattern, and 0.98 (95% CI: 0.95, 1.01) for the FD pattern. Results were consistent when pregnancy loss was classified as either a spontaneous abortion (loss at <20 wk) or a stillbirth (loss at ≥20 wk). CONCLUSION:Prepregnancy adherence to several dietary patterns was not associated with risk of pregnancy loss. 10.3945/ajcn.114.083634
    Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis. Sermondade Nathalie,Huberlant Stéphanie,Bourhis-Lefebvre Vanessa,Arbo Elisangela,Gallot Vanessa,Colombani Marina,Fréour Thomas Human reproduction update BACKGROUND:A worldwide increase in the prevalence of obesity has been observed in the past three decades, particularly in women of reproductive age. Female obesity has been clearly associated with impaired spontaneous fertility, as well as adverse pregnancy outcomes. Increasing evidence in the literature shows that obesity also contributes to adverse clinical outcomes following in vitro fertilization (IVF) procedures. However, the heterogeneity of the available studies in terms of populations, group definition and outcomes prevents drawing firm conclusions. A previous meta-analysis published in 2011 identified a marginal but significant negative effect of increased female body mass index (BMI) on IVF results, but numerous studies have been published since then, including large cohort studies from national registries, highlighting the need for an updated review and meta-analysis. OBJECTIVE AND RATIONALE:Our systematic review and meta-analysis of the available literature aims to evaluate the association of female obesity with the probability of live birth following IVF. Subgroup analyses according to ovulatory status, oocyte origin, fresh or frozen-embryo transfer and cycle rank were performed. SEARCH METHODS:A systematic review was performed using the following key words: ('obesity', 'body mass index', 'live birth', 'IVF', 'ICSI'). Searches were conducted in MEDLINE, EMBASE, Cochrane Library, Eudract and clinicaltrial.gov from 01 January 2007 to 30 November 2017. Study selection was based on title and abstract. Full texts of potentially relevant articles were retrieved and assessed for inclusion by two reviewers. Subsequently, quality was assessed using the Newcastle-Ottawa Quality Assessment Scales for patient selection, comparability and assessment of outcomes. Two independent reviewers carried out study selection and data extraction according to Cochrane methods. Random-effect meta-analysis was performed using Review Manager software on all data (overall analysis), followed by subgroup analyses. OUTCOMES:A total of 21 studies were included in the meta-analysis. A decreased probability of live birth following IVF was observed in obese (BMI ≥ 30 kg/m2) women when compared with normal weight (BMI 18.5-24.9 kg/m2) women: risk ratio (RR) (95% CI) 0.85 (0.82-0.87). Subgroups analyses demonstrated that prognosis was poorer when obesity was associated with polycystic ovary syndrome, while the oocyte origin (donor or non-donor) did not modify the overall interpretation. WIDER IMPLICATIONS:Our meta-analysis clearly demonstrates that female obesity negatively and significantly impacts live birth rates following IVF. Whether weight loss can reverse this deleterious effect through lifestyle modifications or bariatric surgery should be further evaluated. 10.1093/humupd/dmz011
    Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial. Einarsson Snorri,Bergh Christina,Friberg Britt,Pinborg Anja,Klajnbard Anna,Karlström Per-Olof,Kluge Linda,Larsson Ingrid,Loft Anne,Mikkelsen-Englund Anne-Lis,Stenlöf Kaj,Wistrand Anna,Thurin-Kjellberg Ann Human reproduction (Oxford, England) STUDY QUESTION:Does an intensive weight reduction programme prior to IVF increase live birth rates for infertile obese women? SUMMARY ANSWER:An intensive weight reduction programme resulted in a large weight loss but did not substantially affect live birth rates in obese women scheduled for IVF. WHAT IS ALREADY KNOWN:Among obese women, fertility and obstetric outcomes are influenced negatively with increased risk of miscarriage and a higher risk of maternal and neonatal complications. A recent large randomized controlled trial found no effect of lifestyle intervention on live birth in infertile obese women. STUDY DESIGN, SIZE, DURATION:A prospective, multicentre, randomized controlled trial was performed between 2010 and 2016 in the Nordic countries. In total, 962 women were assessed for eligibility and 317 women were randomized. Computerized randomization with concealed allocation was performed in the proportions 1:1 to one of two groups: weight reduction intervention followed by IVF-treatment or IVF-treatment only. One cycle per patient was included. PARTICIPANTS/MATERIALS, SETTING, METHODS:Nine infertility clinics in Sweden, Denmark and Iceland participated. Women under 38 years of age planning IVF, and having a BMI ≥30 and <35 kg/m2 were randomized to two groups: an intervention group (160 patients) with weight reduction before IVF, starting with 12 weeks of a low calorie liquid formula diet (LCD) of 880 kcal/day and thereafter weight stabilization for 2-5 weeks, or a control group (157 patients) with IVF only. MAIN RESULTS AND ROLE OF CHANCE:In the full analysis set (FAS), the live birth rate was 29.6% (45/152) in the weight reduction and IVF group and 27.5% (42/153) in the IVF only group. The difference was not statistically significant (difference 2.2%, 95% CI: 12.9 to -8.6, P = 0.77). The mean weight change was -9.44 (6.57) kg in the weight reduction and IVF group as compared to +1.19 (1.95) kg in the IVF only group, being highly significant (P < 0.0001). Significantly more live births were achieved through spontaneous pregnancies in the weight reduction and IVF group, 10.5% (16) as compared to the IVF only group 2.6% (4) (P = 0.009). Miscarriage rates and gonadotropin dose used for IVF stimulation did not differ between groups. Two subgroup analyses were performed. The first compared women with PCOS in the two randomized groups, and the second compared women in the weight reduction group reaching BMI ≤ 25 kg/m2 or reaching a weight loss of at least five BMI units to the IVF only group. No statistical differences in live birth rates between the groups in either subgroup analysis were found. LIMITATIONS, REASON FOR CAUTION:The study was not powered to detect a small increase in live births due to weight reduction and was not blinded for the patients or physician. Further, the intervention group had a longer time to achieve a spontaneous pregnancy, but were therefore slightly older than the control group at IVF. The study only included women with a BMI lower than 35 kg/m2. WIDER IMPLICATIONS OF THE FINDINGS:The study suggests that weight loss for obese women (BMI: 30-34.9 kg/m2) may not rectify the outcome in IVF cycles, although a significant higher number of spontaneous conceptions occurred in the weight loss group. Also, the study suggests that intensive weight reduction with LCD treatment does not negatively affects the results. STUDY FUNDING/COMPETING INTEREST(S):The study was funded by Sahlgrenska University Hospital (ALFGBG-70 940), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Impolin AB, Hjalmar Svensson Foundation and Jane and Dan Olsson Foundation. Dr Thurin-Kjellberg reports grants from Merck, non-financial support from Impolin AB, during the conduct of the study, and personal fees from Merck outside the submitted work. Dr Friberg reports personal fees from Ferring, Merck, MSD, Finox and personal fees from Studentlitteratur, outside the submitted work. Dr Englund reports personal fees from Ferring, and non-financial support from Merck, outside the submitted work. Dr Bergh reports and has been reimbursed for: writing a newsletter twice a year (Ferring), lectures (Ferring, MSD, Merck), and Nordic working group meetings (Finox). Dr Karlström reports lectures (Ferring, Finox, Merck, MSD) and Nordic working group meetings (Ferring). Ms Kluge, Dr Einarsson, Dr Pinborg, Dr Klajnbard, Dr Stenlöf, Dr Larsson, Dr Loft and Dr Wistrand have nothing to disclose. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov number, NCT01566929. TRIAL REGISTRATION DATE:23-03-2012. DATE OF FIRST PATIENT'S ENROLMENT:05-10-2010. 10.1093/humrep/dex235
    Cost-effectiveness analysis of lifestyle intervention in obese infertile women. van Oers A M,Mutsaerts M A Q,Burggraaff J M,Kuchenbecker W K H,Perquin D A M,Koks C A M,van Golde R,Kaaijk E M,Schierbeek J M,Klijn N F,van Kasteren Y M,Land J A,Mol B W J,Hoek A,Groen H, Human reproduction (Oxford, England) STUDY QUESTION:What is the cost-effectiveness of lifestyle intervention preceding infertility treatment in obese infertile women? SUMMARY ANSWER:Lifestyle intervention preceding infertility treatment as compared to prompt infertility treatment in obese infertile women is not a cost-effective strategy in terms of healthy live birth rate within 24 months after randomization, but is more likely to be cost-effective using a longer follow-up period and live birth rate as endpoint. WHAT IS KNOWN ALREADY:In infertile couples, obesity decreases conception chances. We previously showed that lifestyle intervention prior to infertility treatment in obese infertile women did not increase the healthy singleton vaginal live birth rate at term, but increased natural conceptions, especially in anovulatory women. Cost-effectiveness analyses could provide relevant additional information to guide decisions regarding offering a lifestyle intervention to obese infertile women. STUDY DESIGN, SIZE, DURATION:The cost-effectiveness of lifestyle intervention preceding infertility treatment compared to prompt infertility treatment was evaluated based on data of a previous RCT, the LIFEstyle study. The primary outcome for effectiveness was the vaginal birth of a healthy singleton at term within 24 months after randomization (the healthy live birth rate). The economic evaluation was performed from a hospital perspective and included direct medical costs of the lifestyle intervention, infertility treatments, medication and pregnancy in the intervention and control group. In addition, we performed exploratory cost-effectiveness analyses of scenarios with additional effectiveness outcomes (overall live birth within 24 months and overall live birth conceived within 24 months) and of subgroups, i.e. of ovulatory and anovulatory women, women <36 years and ≥36 years of age and of completers of the lifestyle intervention. Bootstrap analyses were performed to assess the uncertainty surrounding cost-effectiveness. PARTICIPANTS/MATERIALS, SETTINGS, METHODS:Infertile women with a BMI of ≥29 kg/m2 (no upper limit) were allocated to a 6-month lifestyle intervention programme preceding infertility treatment (intervention group, n = 290) or to prompt infertility treatment (control group, n = 287). After excluding women who withdrew informed consent or who were lost to follow-up we included 280 women in the intervention group and 284 women in the control group in the analysis. MAIN RESULTS AND THE ROLE OF CHANCE:Total mean costs per woman in the intervention group within 24 months after randomization were €4324 (SD €4276) versus €5603 (SD €4632) in the control group (cost difference of -€1278, P < 0.05). Healthy live birth rates were 27 and 35% in the intervention group and the control group, respectively (effect difference of -8.1%, P < 0.05), resulting in an incremental cost-effectiveness ratio of €15 845 per additional percentage increase of the healthy live birth rate. Mean costs per healthy live birth event were €15 932 in the intervention group and €15 912 in the control group. Exploratory scenario analyses showed that after changing the effectiveness outcome to all live births conceived within 24 months, irrespective of delivery within or after 24 months, cost-effectiveness of the lifestyle intervention improved. Using this effectiveness outcome, the probability that lifestyle intervention preceding infertility treatment was cost-effective in anovulatory women was 40%, in completers of the lifestyle intervention 39%, and in women ≥36 years 29%. LIMITATIONS, REASONS FOR CAUTION:In contrast to the study protocol, we were not able to perform the analysis from a societal perspective. Besides the primary outcome of the LIFEstyle study, we performed exploratory analyses using outcomes observed at longer follow-up times and we evaluated subgroups of women; the trial was not powered on these additional outcomes or subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS:Cost-effectiveness of a lifestyle intervention is more likely for longer follow-up times, and with live births conceived within 24 months as the effectiveness outcome. This effect was most profound in anovulatory women, in completers of the lifestyle intervention and in women ≥36 years old. This result indicates that the follow-up period of lifestyle interventions in obese infertile women is important. The scenario analyses performed in this study suggest that offering and reimbursing lifestyle intervention programmes in certain patient categories may be cost-effective and it provides directions for future research in this field. STUDY FUNDING/COMPETING INTEREST(S):The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The department of obstetrics and gynaecology of the UMCG received an unrestricted educational grant from Ferring pharmaceuticals BV, The Netherlands. B.W.J.M. is a consultant for ObsEva, Geneva. TRIAL REGISTRATION NUMBER:The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530). http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 1530. 10.1093/humrep/dex092
    Successful weight loss interventions before in vitro fertilization: fat chance? Norman Robert J,Mol Ben Willem J Fertility and sterility Most expert opinions and guidelines indicate the necessity for weight loss before in vitro fertilization (IVF) in women who are overweight or obese. This is based on the documented impact of obesity on pregnancy rates and pregnancy complications and the long-term impact on the child in natural conceptions. Some clinicians and authorities refuse to treat patients unless they are below a certain body mass index. In the past this advice has been hindered by a lack of opportunity for patients to join lifestyle programs and the high dropout failure before treatment. However, the ideal has remained in the search for effective methods for weight loss. New clinical trials have evaluated a lifestyle program before IVF treatment and compared the results with those who were merely given advice and allowed to proceed directly to other fertility treatments or IVF. No compelling evidence of the value of lifestyle intervention for weight loss on live-birth rates was gained from these well-conducted studies. The research and medical and ethical opinions may now favor moving to fertility treatment earlier than originally recommended for patients who are overweight or obese. 10.1016/j.fertnstert.2018.05.029