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01-03-2019 | Obesity | Gynecologic Endocrinology and Reproductive Medicine

PGR and PTX3 gene expression in cumulus cells from obese and normal weighting women after administration of long-acting recombinant follicle-stimulating hormone for controlled ovarian stimulation

Authors: Tanja Burnik Papler, Eda Vrtačnik Bokal, Uršula Prosenc Zmrzljak, Martin Stimpfel, Antonio Simone Laganà, Fabio Ghezzi, Nina Jančar

Published in: Archives of Gynecology and Obstetrics | Issue 3/2019

Abstract

Purpose

The present study aimed to determine clinical IVF parameters and gene expression in cumulus cells (CCs) in obese and normal weighting women after administration of 150 mcg of corifollitropin alfa for controlled ovarian hyperstimulation (COH).

Methods

150 mcg of corifollitropin alfa and gonadotropin releasing hormone antagonist were used for COH. Analysis of CC gene expression was performed using quantitative real-time PCR.

Results

We did not find significant differences in biochemical and clinical pregnancy rates between obese and normal weighting women. Obese women required twice as much of additional gonadotropins for ovarian stimulation and had a significantly lower proportion of good quality embryos on day 5 of IVF cycle. Expression of PGR and PTX3 was significantly higher in CCs of obese women.

Conclusion

Obese women require significantly larger amounts of gonadotropins to achieve similar IVF success rates as normal weighting women. Differences in CC gene expression and smaller proportion of good quality embryos may imply that oocytes derived from obese women are of lower quality. Further studies are needed to evaluate whether obesity itself or the higher amount of gonadotropins used in obese women causes this effect.

WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 894:i–xii(1-253)

Balen AH, Anderson RA (2007) Impact of obesity on female reproductive health: British Fertility Society, Policy and Practice Guidelines. Hum Fertil (Camb) 10:195–206. https://doi.org/10.1080/14647270701731290 CrossRef

Gesink Law DC, Maclehose RF, Longnecker MP (2007) Obesity and time to pregnancy. Hum Reprod 22:414–420. https://doi.org/10.1093/humrep/del400 CrossRefPubMed

Kumbak B, Oral E, Bukulmez O (2012) Female obesity and assisted reproductive technologies. Semin Reprod Med 30:507–516. https://doi.org/10.1055/s-0032-1328879 CrossRefPubMed

Shah DK, Missmer SA, Berry KF, Racowsky C, Ginsburg ES (2011) Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization. Obstet Gynecol 118:63–70. https://doi.org/10.1097/AOG.0b013e31821fd360 CrossRefPubMed

Wei S, Schmidt MD, Dwyer T, Norman RJ, Venn AJ (2009) Obesity and menstrual irregularity: associations with SBHG, testosterone and insulin. Obesity 17:1070–1076. https://doi.org/10.1038/oby.2008.641 CrossRefPubMed

Metwally M, Cutting R, Tipton A, Skull J, Ledger WL, Li TC (2007) Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod Biomed Online 15:532–538CrossRefPubMed

Rhee JS, Saben JL, Mayer AL, Schulte MB, Asghar Z, Stephens C et al (2016) Diet-induced obesity impairs endometrial stromal cell decidualization: a potential role for impaired autophagy. Hum Reprod 31:1315–1326. https://doi.org/10.1093/humrep/dew048 CrossRefPubMedPubMedCentral

Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R (2010) Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum Reprod 26:245–252. https://doi.org/10.1093/humrep/deq306 CrossRefPubMed

10.

Cardozo ER, Karmon AE, Gold J, Petrozza JC, Styer AK (2016) Reproductive outcomes in oocyte donation cycles are associated with donor BMI. Hum Reprod 31:385–392. https://doi.org/10.1093/humrep/dev298 CrossRefPubMed

11.

Matzuk MM, Burns KH, Viveiros MM, Eppig JJ (2002) Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 296:2178–2180. https://doi.org/10.1126/science.1071965 CrossRef

12.

Assou S, Haouzi D, De Vos J, Hamamah S (2010) Human cumulus cells as biomarkers for embryo and pregnancy outcomes. Mol Hum Reprod 16:531–538. https://doi.org/10.1093/molehr/gaq032 CrossRefPubMed

13.

Cillo F, Brevini TA, Antonini S, Paffoni A, Ragni G, Gandolfi F (2007) Association between human oocyte developmental competence and expression levels of some cumulus genes. Reproduction 134:645–650. https://doi.org/10.1530/REP-07-0182 CrossRefPubMed

14.

McKenzie LJ, Pangas SA, Carson SA, Kovanci E, Cisneros P, Buster JE et al (2004) Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Hum Reprod 19:2869–2874. https://doi.org/10.1093/humrep/deh535 CrossRefPubMed

15.

Zhang X, Jafari N, Barnes RB, Confino E, Milad M, Kazer RR (2005) Studies of gene expression in human cumulus cells indicate pentraxin 3 as a possible marker for oocyte quality. Fertil Steril 83(Suppl 1):1169–1179. https://doi.org/10.1016/j.fertnstert.2004.11.030 CrossRefPubMed

16.

Huang X, Hao C, Shen X, Zhang Y, Liu X (2013) RUNX2, GPX3 and PTX3 gene expression profiling in cumulus cells are reflective of oocyte/embryo competence and potentially reliable predictors of embryo developmental competence in PCOS patients. Reprod Biol Endocrinol 11:109. https://doi.org/10.1186/1477-7827-11-109 CrossRefPubMedPubMedCentral

17.

van Montfoort AP, Geraedts JP, Dumoulin JC, Stassen AP, Evers JL, Ayoubi TA (2008) Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis. Mol Hum Reprod 14:157–168. https://doi.org/10.1093/molehr/gam088 CrossRefPubMed

18.

Wathlet S, Adriaenssens T, Segers I, Verheyen G, Van de Velde H, Coucke W et al (2011) Cumulus cell gene expression predicts better cleavage-stage embryo or blastocyst development and pregnancy for ICSI patients. Hum Reprod 26:1035–1051. https://doi.org/10.1093/humrep/der036 CrossRefPubMed

19.

Adriaenssens T, Wathlet S, Segers I, Verheyen G, Devos A, Van der Elst J et al (2010) Cumulus cell gene expression is associated with oocyte developmental quality and influenced by patient and treatment characteristics. Hum Reprod 25:1259–1270. https://doi.org/10.1093/humrep/deq049 CrossRefPubMed

20.

Devjak R, Fon Tacer K, Juvan P, Virant Klun I, Rozman D, Vrtačnik Bokal E (2012) Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist. PLoS One 7:e47106. https://doi.org/10.1371/journal.pone.0047106 CrossRefPubMedPubMedCentral

21.

Wathlet S, Adriaenssens T, Segers I, Verheyen G, Van Landuyt L, Coucke W et al (2013) Pregnancy prediction in single embryo transfer cycles after ICSI using QPCR: validation in oocytes from the same cohort. PLoS One 8:e54226. https://doi.org/10.1371/journal.pone.0054226 CrossRefPubMedPubMedCentral

22.

Balen AH, Platteau P, Andersen AN, Devroey P, Sørensen P, Helmgaard L et al (2006) The influence of body weight on response to ovulation induction with gonadotrophins in 335 women with World Health Organization group II anovulatory infertility. BJOG 113:1195–1202. https://doi.org/10.1111/j.1471-0528.2006.01034.x CrossRefPubMed

23.

Maheshwari A, Stofberg L, Bhattacharya S (2007) Effect of overweight and obesity on assisted reproductive technology—a systematic review. Hum Reprod Update 13:433–444. https://doi.org/10.1093/humupd/dmm017 CrossRefPubMed

24.

Fauser BC, Mannaerts BM, Devroey P, Leader A, Boime I, Baird DT (2009) Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency. Hum Reprod Update 15:309–321. https://doi.org/10.1093/humupd/dmn065 CrossRefPubMed

25.

de Greef R, Zandvliet AS, de Haan AF, Ijzerman-Boon PC, Marintcheva-Petrova M, Mannaerts BM (2010) Dose selection of corifollitropin alfa by modeling and simulation in controlled ovarian stimulation. Clin Pharmacol Ther 88:79–87. https://doi.org/10.1038/clpt.2010.54 CrossRefPubMed

26.

Corifollitropin Alfa Ensure Study Group (2010) Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women. Reprod Biomed Online 21:66–76. https://doi.org/10.1016/j.rbmo.2010.03.019 CrossRef

27.

Ledger WL, Fauser BC, Devroey P, Zandvliet AS, Mannaerts BM (2011) Corifollitropin alfa doses based on body weight: clinical overview of drug exposure and ovarian response. Reprod Biomed Online 23:150–159. https://doi.org/10.1016/j.rbmo.2011.04.002 CrossRefPubMed

28.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262 CrossRef

29.

Fensore S, Di Marzio M, Tiboni GM (2015) Corifollitropin alfa compared to daily FSH in controlled ovarian stimulation for in vitro fertilization: a meta-analysis. J Ovarian Res 8:33–40. https://doi.org/10.1186/s13048-015-0160-4 CrossRefPubMedPubMedCentral

30.

Souter I, Baltagi LM, Kuleta D, Meeker JD, Petrozza JC (2011) Women, weight, and fertility: the effect of body mass index on the outcome of superovulation/intrauterine insemination cycles. Fertil Steril 95:1042–1047. https://doi.org/10.1016/j.fertnstert.2010.11.062 CrossRefPubMed

31.

Ozekinci M, Seven A, Olgan S, Sakinci M, Keskin U, Akar ME et al (2015) Does obesity have detrimental effects on IVF treatment outcomes? BMC Womens Health 15:61–67. https://doi.org/10.1186/s12905-015-0223-0 CrossRefPubMedPubMedCentral

32.

Esinler I, Bozdag G, Yarali H (2008) Impact of isolated obesity on ICSI outcome. Reprod Biomed Online 17:583–587CrossRefPubMed

33.

Yamamoto D, Yasui T, Kobayashi C, Kitazato T, Iwasa T, Irahara M (2016) Effect of high fat diet on artificial oocyte activation following superovulation in mice. Zygote 24:286–292. https://doi.org/10.1017/S0967199415000192 CrossRefPubMed

34.

Bermejo-Alvarez P, Rosenfeld CS, Roberts RM (2012) Effect of maternal obesity on estrous cyclicity, embryo development and blastocyst gene expression in a mouse model. Hum Reprod 27:3513–3522. https://doi.org/10.1093/humrep/des327 CrossRefPubMedPubMedCentral

35.

Bellver J, Ayllón Y, Ferrando M, Melo M, Goyri E, Pellicer A et al (2010) Female obesity impairs in vitro fertilization outcome without affecting embryo quality. Fertil Steril 93:447–454. https://doi.org/10.1016/j.fertnstert.2008.12.032 CrossRefPubMed

36.

Salha O, Dada T, Sharma V (2001) Influence of body mass index and self administration of hCG on the outcome of IVF cycles: a prospective cohort study. Hum Fertil (Camb) 4:37–42CrossRef

37.

van Swieten EC, van der Leeuw-Harmsen L, Badings EA, van der Linden PJ (2005) Obesity and clomiphene challenge test as predictors of outcome of in vitro fertilization and intracytoplasmic sperm injection. Gynecol Obst Invest 59:220–224. https://doi.org/10.1159/000084347 CrossRef

38.

Zhang D, Zhu Y, Gao H, Zhou B, Zhang R, Wang T et al (2010) Overweight and obesity negatively affect the outcomes of ovarian stimulation and in vitro fertilisation: a cohort study of 2628 Chinese women. Gynecol Endocrinol 26:325–332. https://doi.org/10.3109/09513591003632100 CrossRefPubMed

39.

Minge CE, Bennett BD, Norman RJ, Robker RL (2008) Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality. Endocrinology 149:2646–2656. https://doi.org/10.1210/en.2007-1570 CrossRefPubMed

40.

Zhang JJ, Feret M, Chang L, Yang M, Merhi Z (2015) Obesity adversely impacts the number and maturity of oocytes in conventional IVF not in minimal stimulation IVF. Gynecol Endocrinol 31:409–413. https://doi.org/10.3109/09513590.2015.1014785 CrossRefPubMed

41.

Santos MA, Kuijk EW, Macklon NS (2010) The impact of ovarian stimulation for IVF on the developing embryo. Reproduction 139:23–34. https://doi.org/10.1530/REP-09-0187 CrossRefPubMed

42.

Farhi J, Ben-Haroush A, Sapir O, Fisch B, Ashkenazi J (2010) High-quality embryos retain their implantation capability in over-weight women. Reprod Biomed Online 21:706–711. https://doi.org/10.1016/j.rbmo.2010.06.040 CrossRefPubMed

43.

Rittenberg V, Seshadri S, Sunkara SK, Sobaleva S, Oteng-Ntim E, El-Toukhy T (2011) Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online 23:421–439. https://doi.org/10.1016/j.rbmo.2011.06.018 CrossRefPubMed

44.

Varani S, Elvin JA, Yan C, De Mayo J, De Mayo FJ, Horton HF et al (2002) Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol 16:1154–1167. https://doi.org/10.1210/mend.16.6.0859 CrossRefPubMed

45.

Buccione R, Vanderhyden BC, Caron PJ, Eppig JJ (1990) FSH-induced expansion of the mouse cumulus oophorus in vitro is dependent upon a specific factor(s) secreted by the oocyte. Dev Biol 138:16–25CrossRef

46.

Salustri A, Garlanda C, Hirsch E, De Acetis M, Maccagno A, Bottazzi B et al (2004) PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in vivo fertilization. Development 131:1577–1586. https://doi.org/10.1242/dev.01056 CrossRefPubMed

47.

Wu LL, Russell DL, Norman RJ, Robker RL (2012) Endoplasmic reticulum (ER) stress in cumulus–oocyte complexes impairs pentraxin-3 secretion, mitochondrial membrane potential (DeltaPsi m), and embryo development. Mol Endocrinol 26:562–573. https://doi.org/10.1210/me.2011-1362 CrossRefPubMedPubMedCentral

48.

Morgan PM, Boatman DE, Bavister BD (1990) Relationships between follicular fluid steroid hormone concentrations, oocyte maturity, in vitro fertilization and embryonic development in the rhesus monkey. Mol Reprod Dev 27:145–151CrossRefPubMed

49.

Eroglu A (1993) Experimental studies on in vitro maturation of porcine oocytes. II. Effects of estradiol-17 beta and progesterone. Berl Munch Tierarztl Wochenschr 106:157–159PubMed

50.

Revelli A, Pacchioni D, Cassoni P, Bussolati G, Massobrio M (1996) In situ hybridization study of messenger RNA for estrogen receptor and immunohistochemical detection of estrogen and progesterone receptors in the human ovary. Gynecol Endocrinol 10:177–186CrossRefPubMed

51.

Shimada M, Terada T (2002) FSH and LH induce progesterone production and progesterone receptor synthesis in cumulus cells: a requirement for meiotic resumption in porcine oocytes. Mol Hum Reprod 8:612–618CrossRefPubMed

52.

Hasegawa J, Yanaihara A, Iwasaki S, Otsuka Y, Negishi M, Akahane T et al (2005) Reduction of progesterone receptor expression in human cumulus cells at the time of oocyte collection during IVF is associated with good embryo quality. Hum Reprod 20:2194–2200. https://doi.org/10.1093/humrep/dei005 CrossRefPubMed

Title: PGR and PTX3 gene expression in cumulus cells from obese and normal weighting women after administration of long-acting recombinant follicle-stimulating hormone for controlled ovarian stimulation
Authors: Tanja Burnik Papler
Eda Vrtačnik Bokal
Uršula Prosenc Zmrzljak
Martin Stimpfel
Antonio Simone Laganà
Fabio Ghezzi
Nina Jančar
Publication date: 01-03-2019
Publisher: Springer Berlin Heidelberg
Keywords: Obesity
Obesity
Published in: Archives of Gynecology and Obstetrics / Issue 3/2019
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-018-5031-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

PGR and PTX3 gene expression in cumulus cells from obese and normal weighting women after administration of long-acting recombinant follicle-stimulating hormone for controlled ovarian stimulation

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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