Analysis of factors associated with ovarian reserve in a group of poor responders to in vitro fertilization: A cross-sectional study


Background: Poor ovarian reserve and a high rate of pregnancy failure associated with low quality and quantity of oocytes are observed in poor responders to in vitro fertilization.

Objective: To assess the effect of age, body mass index (BMI), endometriosis, and history of ovarian surgery on ovarian reserve in a group of poor responders.

Materials and Methods: In this cross-sectional study 749 women who referred to Yasmin Clinic of Dr Cipto Mangunkusumo National General Hospital from January 2013 to June 2017 were enrolled. Two definitions of poor responders and Poseidon criteria and consecutive sampling techniques were used. Participants were divided into good and poor responder groups based on the ovarian reserve test; participant with oocyte ≤ 3 was classified as a poor responder. Based on this, 188 participants with nine (4-47) oocytes were included in the poor responder group. While good responder comprised of two (0-3) oocytes.

Results: Age and anti-Mullerian hormone level (AMH) were significantly associated with ovarian reserve in the poor-responder group (p < 0.001). However, in multivariate analyses, age was the only significant predictor of ovarian response in the poor responder group (p = 0.004). While endometriosis was the significant predictor of Poseidon groups 1 and 4, surgical history was the significant predictor of Poseidon groups 2 and 3. Meanwhile, an increase in BMI decreased the risk of classification under Poseidon group 3.

Conclusion: Age, AMH, BMI, endometriosis, and history of ovarian surgery affected the risk of classification of the Poseidon group.

Key words: Ovarian reserve, Poseidon, In vitro fertilization.

[1] Stern K. Assisted reproductive technology: What’s new and what’s important? Aust Fam Physician 2012; 41: 762– 768.

[2] Ferraretti AP, Marca AL, Fauser B, Tarlatzis B, Nargund G, Gianaroli L. ESHRE consensus on the definition of “poor response” to ovarian stimulation for in vitro fertilization: The bologna criteria. Hum Reprod 2011; 26: 1616–1624.

[3] Liu KE, Case A. Advanced reproductive age and fertility. J Obstet Gynaecol Can 2011; 33: 1165–1167.

[4] Disseldorp JV, Eijkemans R, Fauser B, Broekmans F. Hypertensive pregnancy complications in poor and normal responders after in vitro fertilization. Fertil Steril 2010; 93: 652–657.

[5] Mouzon Jd, Goossens V, Bhattacharya S, Castilla JA, Ferraretti AP, Korsak V, et al. Assisted reproductive technology in Europe, 2006: Results generated from European registers by ESHRE. Hum Reprod 2010; 25: 1851–1162.

[6] PERFITRI. Laporan IVF di Indonesia [unpublished organization report]. Perhimpunan Fertilisasi In Vitro Indonesia; 2012.

[7] Yasmin IVF Clinic. Laporan Tahunan Klinik Yasmin [unpublished clinic report]. Klinik Yasmin, Dr.Cipto Mangunkusumo General Hospital; 2014.

[8] Yasmin IVF Clinic. Laporan Tahunan Klinik Yasmin [unpublished clinic report]. Klinik Yasmin, Dr.Cipto Mangunkusumo General Hospital; 2015.

[9] Fauser BCJM, Diedrich K, Devroey P, Evian Annual Reproduction Workshop Group 2007. Predictors ov ovarian response: Progress towards individualized treatment in ovulation induction and ovarian stimulation. Hum Reprod Update 2008; 14: 1–14.

[10] Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Repod Update 2006; 12: 685–718.

[11] Broekmans FJ, Knauff EAH, te Velde ER, Macklon NS, Fauser BC. Female reproductive ageing: Current knowledge and future trends. Trends Endocrinol Metab 2007; 18: 58–65.

[12] Findlay JK, Hutt KJ, Hickey M, Anderson RA. What is the “ovarian reserve”? Fertil Steril 2015; 103: 628–630.

[13] Wiweko B, Hestiantoro A, Sumapraja K, Natadisastra M, Febia E, Andriyana H, et al. Anti mullerian hormone serum level indicates ovarian response in controlled ovarian hyperstimulation of IVF Cycles. Indones J Obstet Gynecol 2010; 34: 114–118.

[14] Padhy N, Gupta S, Mahla A, Latha M, Varma T. Demographic characteristic and clinical profile of poor responders in IVF/ ICSI: A comparative study. J Hum Reprod Sci 2012; 3: 91–94.

[15] Ubaldi F, Vaiarelli A, D Anna R, Rienzi L. Management of poor responders in IVF: Is there anything new? BioMed Res Int 2014; 2014: 1–11.

[16] Fritz MA, Speroff L. Clinical gynecology endocrinology and infertility. Philadelphia: Lippincott Williams & Wilkins; 2011: 107–113.

[17] Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri A. Obesity and reproductive disorders in women. Hum Reprod Update 2003; 9: 359–372.

[18] Kitajima M, Defrere S, Dolmans MM, Colette S, Squifflet J, Langendonckt AV, et al. Endometriomas as a possible cause of reduced ovarian reserve in women with endometriosis. Fertil Steril 2011; 96: 685–691.

[19] Kitajima M, Masuzaki H. Ovarian reserve in patients with endometriosis. In Harada T, editor. Endometriosis: Pathogenesis and Treatment. 26th chapter. Japan: Springer; 2014. 419–429.

[20] Alviggi C, Andersen CY, Buehler K, Conforti A, De Placido G, Esteves SC, et al. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. Fertil Steril 2016; 105: 1452–1453.

[21] Humaidan P, Alviggi C, Fischer R, Esteves SC. The novel POSEIDON stratification of ’ Low prognosis patients in Assisted Reproductive Technology’ and its proposed marker of successful outcome. F10000Res 2016; 5: 2911– 2921.

[22] Halawaty S, ElKattan E, Azab H, ElGhamry N, Al-Inany H. Effect of obesity on parameters of ovarian reserve in premenopausal women. J Obstet Gynaecol Can 2010; 32: 687–690.

[23] Wiweko B, Maidarti M, Priangga MD, Shafira N, Fernando D, Sumapraja K, et al. Anti-mullerian hormone as a diagnostic and prognostic tool for PCOS patients. J Assist Reprod Genet 2014; 31: 1311–1316.

[24] Fruzzetti F, Perini D, Lazzarini V, Parrini D, Genazzani AR. Adolescent girls with polycystic ovary syndrome showing different phenotypes have a different metabolic profile associated with increasing androgen levels. Fertil Steril 2009; 92: 626–634.

[25] Freeman EW, Gracia CR, Sammel MD, Lin H, Lim LCL, Strauss JF. Association of AMH levels with obesity in late reproductive age women. Fertil Steril 2007; 87: 101–106.

[26] De Pergola G, Maldera S, Tartagni M, Pannacciulli N, Loverro G, Giorgino R. Inhibitory effect of obesity on gonadotropin, estradiol, and inhibin B Levels in fertile women. Obesity (Silver Spring) 2006; 14: 1954–1960.

[27] Su HI, Sammel MD, Freeman EW, Lin H, DeBlasis T, Gracia CR. Body size affects measures of ovarian reserve in late reproductive age women. Menopause 2008; 15: 857– 861.

[28] Lemos NA, Arbo E, Scalco R, Weiler E, Rosa V, Cunha-Filho JS. Decreased antimüllerian hormone and altered ovarian follicular cohort in infertile patients with mild/minimal endometriosis. Fertil Steril 2008; 89: 1064–1068.

[29] Dokras A, Habana A, Giraldo J, Jones E. Secretion of inhibin B during ovarian stimulation is decreased in infertile women with endometriosis. Fertil Steril 2000; 74: 35–40.

[30] Hwu YM, Wu FSY, Li SH, Sun FJ, Lin MH, Lee RKK. The impact of endometrioma and laparoscopic cystectomy on serum anti-Mullerian hormone levels. Reprod Biol Endocrinol 2011; 9: 80–87.

[31] Uncu G, Kasapoglu I, Ozerkan K, Seyhan A, Oral Yilmaztepe A, Ata B. Prospective assessment of the impact of endometriomas and their removal on ovarian reserve and determinants of the rate of decline in ovarian reserve. Hum Reprod 2013; 28: 2140–2145.

[32] Kitajima M, Newaz Khan K, Harada A, Taniguchi K, Inoue T, Kaneuchi M, et al. Association between ovarian endometrioma and ovarian reserve. Front Biosci 2018; 10: 92–102.

[33] Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril 2012; 98: 591–598.

[34] Lind T, Hammarström M, Lampic C, Rodriguez-Wallberg K. Anti-Müllerian hormone reduction after ovarian cyst surgery is dependent on the histological cyst type and preoperative anti-Müllerian hormone levels. Acta Obstet Gynecol Scand 2015; 94: 183–190.