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Obesity and high fat diet impair response to superovulation by suppressing genes involved in ovarian folliculogenesis
attributes of a health promotion class (HPC) would be attractive to infertility patients. DESIGN: Cross-sectional survey study. MATERIALS AND METHODS: Patients aged 21-35 presenting to an infertility clinic were invited to complete an anonymous survey regarding demographics, perceptions of health, weight status, the effect of excess preconception weight and potential weight optimization interventional components. Data was analyzed using regression models. RESULTS: To date, 24 of the 50 eligible women completed the survey. Women were typically young (30.1 6.5 years), married (87%), Caucasian (78%), and college educated (61%) with average BMI of 32 kg/m2. On a 5point Likert scale, most consider themselves ‘‘somewhat healthy’’ (64%), feel ‘‘very/completely confident’’ (64%) that they could perform moderate physical activity (PA) for 30 minutes 5 times/week, correctly identify PA recommendations (71%) but are aware that they do not meet these recommendations (68%). In preparation for pregnancy, patients indicated they should lose weight (65%) and increase PA (74%), and were aware that excess preconception weight increases the risk of infertility (86%), pregnancy complications (86%), and difficult childbirth (82%), however, only 50% were aware of the increased risk of having an overweight/obese child. Of the 67% of patients who indicated they would attend a health promotion class (HPC), many would attend weekly or monthly meetings (58%) lasting 30-60 minutes (63%) in a community room (42%), gym (42%), online (58%), or via email (46%), without monetary incentive (85%). Most preferred a HPC that would provide tips for cheap, healthy eating including recipes and progress tracking. CONCLUSIONS: Our study demonstrates that infertile patients are aware of the risks of excess weight as well as PA recommendations, but do not meet PA recommendations despite indicating they are physically capable of doing so. A majority of patients would participate in a HPC without incentive. Preferences for frequency, duration, location and type of class identified by this study can be used to develop a HPC tailored to infertility patients. Supported by: Study funded by Virginia Tech Fralin Life Sciences Institute P-46 Tuesday, October 20, 2015 ADOLESCENT BODY MASS INDEX IS DECREASED IN CHILDREN CONCEIVED BY INFERTILE COUPLES, REGARDLESS H. Hanson,b OF FERTILITY TREATMENT. M. Link,a J. M. Hotaling,c K. Smith,d K. Aston,e D. T. Carrell,f E. B. Johnstone.c aObstetrics and Gynecology, University of Utah, Salt Lake City, UT; bFamily and Preventive Medicine, University of Utah, Salt Lake City, UT; cUniversity of Utah, Salt Lake City, UT; dPopulation Sciences, University of Utah, Salt Lake City, UT; eAndrology and IVF Laboratories, University of Utah, Salt Lake City, UT; fUniversity of Utah School of Medicine, Salt Lake City, UT. OBJECTIVE: To determine whether birth weight and adolescent body mass index (BMI) differ among offspring of infertile couples conceived with and without the use of assisted reproductive technologies and whether they differ from offspring of fertile controls. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Children of infertile Utah couples born prior to 1999 were selected for study inclusion (n¼6,251). Data include 165 children conceived through intrauterine insemination (IUI), 224 children conceived through in vitro fertilization (IVF) and 5,862 natural conceptions (Infertile - NC). Offspring of infertile couples were matched to offspring of fertile controls by sex, birth year (+/- 1 year), year of BMI measurement (+/- 2 years), and multiplicity (singleton, multiple birth). Primary outcomes of interest were birth weight and BMI at first driver’s license record. Multivariate generalized linear models were run adjusting for birth order, gestational age, maternal age, maternal/ paternal education, socioeconomic status, and maternal/paternal BMI. RESULTS: Table 1 shows a summary of the results. For singleton births, there were no significant differences in birth weight among IUI/IVF infants, infertile-NC children, and children of fertile couples. BMI in adolescence was lower in singletons conceived through IVF and Infertile-NC children compared to children of fertile controls. For twin births, birth weight was lower for IVF children but there were no other significant differences in birth weight between children of infertile and fertile couples. In adolescence, all twins of infertile couples, regardless of route of conception, had lower BMIs than children of fertile controls. CONCLUSIONS: Twins, and to a lesser degree, singletons born to infertile couples have similar birth weights but slightly lower adolescent BMI than children born to fertile couples, regardless of the route of conception. Factors leading to infertility may contribute to in utero stress that is compounded by twin gestation and may ultimately result in decreased BMI for offspring.
FERTILITY & STERILITYÒ
Table 1 - Birth Weight and Adolescent BMI of Children Born to Infertile and Fertile Couples.
SINGLETONS
TWINS
Birth Weight Adolescent Birth Weight Adolescent (grams) BMI (grams) BMI Children of Fertile Controls Infertile - IUI Infertile - IVF Infertile - NC
3248
21.4
2701
20.0
3255 3245 3242
21.0 20.6* 21.0*
2588 2467* 2607
18.7* 18.5* 19.2*
P-47 Tuesday, October 20, 2015 OBESITY AND HIGH FAT DIET IMPAIR RESPONSE TO SUPEROVULATION BY SUPPRESSING GENES INVOLVED IN OVARIAN FOLLICULOGENESIS. K. Thornton,a O. A. Asemota,b S. K. Jindal,a M. Charron,a E. Buyuk.a aObstetrics and Gynecology, Albert Einstein College of Medicine/ Montefiore Medical Center, Bronx, NY; bAdvanced Fertility Center of Chicago, Gurnee, IL. OBJECTIVE: Obese women undergoing controlled ovarian hyperstimulation (COH) have higher cycle cancellation rates, fewer oocytes collected and lower pregnancy rates. The exact mechanism of how obesity causes reproductive dysfunction is not well understood. We hypothesize that obesity and high fat diet are associated with altered ovarian gene expression, which interferes with folliculogenesis and/or ovulation. DESIGN: Prospective controlled study. MATERIALS AND METHODS: Mice were subjected to dietary manipulation starting at 6w to develop 2 female rodent models: Group 1: C57BL/6J normal chow fed mice (NC) (N¼12) and Group 2: C57BL/6J high fat diet fed mice (HF) (N¼12). At 20w of age, 6 mice in each group were sacrificed while another 6 underwent superovulation (SO) with gonadotropins and then were sacrificed. At the time of sacrifice, one ovary was snap frozen in liquid nitrogen and used for RNA extraction and RT-PCR for detecting the following genes: Gdf-9, Bmp-15, Amh, Amhr (Amh receptor), Foxl2, Gja1 (mouse homolog for human connexin 43), Fshr and Lhcgr. Ribosomal protein 36b4 was used as loading control. Data given as units of expression SEM and p<0.05 was considered significant. RESULTS: HF mice gained significantly more weight than NC mice (26.9g 4.3 vs. 19.1 1.5, p< 0.01). HF mice also produced significantly lower number of oocytes after SO compared to NC mice (6.7 1.8 vs 1.8 0.5, p¼0.04). As expected in NC mice, there was no increase in the genes of early folliculogenesis Gdf-9, Bmp-15 and Foxl2 in response to SO. In contrast, HF mice had significantly decreased expression of Gdf-9 (7.2 1.3 vs 1.7 0.4, p¼0.02) and increased expression of Foxl2 (2.6 0.3 vs 3.7 1, p¼0.02) in response to SO but no change in Bmp15. On the other hand, as expected, genes of late folliculogenesis, Gja1 and Fshr, were significantly increased with SO in NC mice (6.5 2.6 vs 16.6 2.2, p¼ 0.02; 16.0 4 vs 135.3 34.4, p¼0.01; respectively). Surprisingly, in HF mice, there was no increase in the expression of Fshr or Gja1 in response to SO. Finally, Lhcgr was significantly increased with SO in both NC (2.7 1 vs 7.7 1.1, p¼0.03) and HF mice (1.1 0.2 vs 7.2 0.3, p¼0.01). There was no difference in expression of Amh or Amhr with SO in both groups. CONCLUSIONS: HF diet, together with increased adiposity, leads to changes in the expression of genes of early and late folliculogenesis in response to SO. This may contribute to the reproductive dysfunction seen with obesity. Lack of upregulation of Fshr and Gja1 genes may be responsible for decreased oocyte collection seen in HF diet and obesity. P-48 Tuesday, October 20, 2015 OVERWEIGHT AND OBESITY ADVERSELY AFFECT IN VITRO FERTILIZATION (IVF) OUTCOMES IN WOMEN WITH POLYCYSTIC OVARY SYNDROME (PCOS). O. S. Abdalmageed,a,b A. M. Darwish,a S. J. Muasher,b J. Eaton,b S. Keyhan,b S. Abdel-Hamid,a D. J. Raburn,b W. W. Hurd.b aAssiut University IVF Center, Assiut, Egypt; b Duke University, Durham, NC. OBJECTIVE: The effect of overweight and obesity on IVF outcomes is still questionable. The purpose of this study was to determine if overweight/obesity in women with PCOS were associated with an adverse IVF outcome compared to those with normal weight. DESIGN: Retrospective cohort study.
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FERTILITY & STERILITYÒ
Table 1 - Birth Weight and Adolescent BMI of Children Born to Infertile and Fertile Couples.
SINGLETONS
TWINS
Birth Weight Adolescent Birth Weight Adolescent (grams) BMI (grams) BMI Children of Fertile Controls Infertile - IUI Infertile - IVF Infertile - NC
3248
21.4
2701
20.0
3255 3245 3242
21.0 20.6* 21.0*
2588 2467* 2607
18.7* 18.5* 19.2*
P-47 Tuesday, October 20, 2015 OBESITY AND HIGH FAT DIET IMPAIR RESPONSE TO SUPEROVULATION BY SUPPRESSING GENES INVOLVED IN OVARIAN FOLLICULOGENESIS. K. Thornton,a O. A. Asemota,b S. K. Jindal,a M. Charron,a E. Buyuk.a aObstetrics and Gynecology, Albert Einstein College of Medicine/ Montefiore Medical Center, Bronx, NY; bAdvanced Fertility Center of Chicago, Gurnee, IL. OBJECTIVE: Obese women undergoing controlled ovarian hyperstimulation (COH) have higher cycle cancellation rates, fewer oocytes collected and lower pregnancy rates. The exact mechanism of how obesity causes reproductive dysfunction is not well understood. We hypothesize that obesity and high fat diet are associated with altered ovarian gene expression, which interferes with folliculogenesis and/or ovulation. DESIGN: Prospective controlled study. MATERIALS AND METHODS: Mice were subjected to dietary manipulation starting at 6w to develop 2 female rodent models: Group 1: C57BL/6J normal chow fed mice (NC) (N¼12) and Group 2: C57BL/6J high fat diet fed mice (HF) (N¼12). At 20w of age, 6 mice in each group were sacrificed while another 6 underwent superovulation (SO) with gonadotropins and then were sacrificed. At the time of sacrifice, one ovary was snap frozen in liquid nitrogen and used for RNA extraction and RT-PCR for detecting the following genes: Gdf-9, Bmp-15, Amh, Amhr (Amh receptor), Foxl2, Gja1 (mouse homolog for human connexin 43), Fshr and Lhcgr. Ribosomal protein 36b4 was used as loading control. Data given as units of expression SEM and p<0.05 was considered significant. RESULTS: HF mice gained significantly more weight than NC mice (26.9g 4.3 vs. 19.1 1.5, p< 0.01). HF mice also produced significantly lower number of oocytes after SO compared to NC mice (6.7 1.8 vs 1.8 0.5, p¼0.04). As expected in NC mice, there was no increase in the genes of early folliculogenesis Gdf-9, Bmp-15 and Foxl2 in response to SO. In contrast, HF mice had significantly decreased expression of Gdf-9 (7.2 1.3 vs 1.7 0.4, p¼0.02) and increased expression of Foxl2 (2.6 0.3 vs 3.7 1, p¼0.02) in response to SO but no change in Bmp15. On the other hand, as expected, genes of late folliculogenesis, Gja1 and Fshr, were significantly increased with SO in NC mice (6.5 2.6 vs 16.6 2.2, p¼ 0.02; 16.0 4 vs 135.3 34.4, p¼0.01; respectively). Surprisingly, in HF mice, there was no increase in the expression of Fshr or Gja1 in response to SO. Finally, Lhcgr was significantly increased with SO in both NC (2.7 1 vs 7.7 1.1, p¼0.03) and HF mice (1.1 0.2 vs 7.2 0.3, p¼0.01). There was no difference in expression of Amh or Amhr with SO in both groups. CONCLUSIONS: HF diet, together with increased adiposity, leads to changes in the expression of genes of early and late folliculogenesis in response to SO. This may contribute to the reproductive dysfunction seen with obesity. Lack of upregulation of Fshr and Gja1 genes may be responsible for decreased oocyte collection seen in HF diet and obesity. P-48 Tuesday, October 20, 2015 OVERWEIGHT AND OBESITY ADVERSELY AFFECT IN VITRO FERTILIZATION (IVF) OUTCOMES IN WOMEN WITH POLYCYSTIC OVARY SYNDROME (PCOS). O. S. Abdalmageed,a,b A. M. Darwish,a S. J. Muasher,b J. Eaton,b S. Keyhan,b S. Abdel-Hamid,a D. J. Raburn,b W. W. Hurd.b aAssiut University IVF Center, Assiut, Egypt; b Duke University, Durham, NC. OBJECTIVE: The effect of overweight and obesity on IVF outcomes is still questionable. The purpose of this study was to determine if overweight/obesity in women with PCOS were associated with an adverse IVF outcome compared to those with normal weight. DESIGN: Retrospective cohort study.
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