Published: 2021-06-28

Study of patients with diminished ovarian reserve and our approach to their treatment: retrospective analytic study

Sujoy Mitra, Sangisapu Srinivas, Baidyanath Pathak, Uttara Aiyyer, Deepak Patil


Background: Diminished ovarian reserve (DOR) is a perplexing entity. For the physician, optimisation of all aspects of management is needed to fruitfully utilise the available pool of gametes and time.

Methods: In this multicentric retrospective analytic study, we re-evaluated all cases of DOR. All aspects of management were critically assessed.

Results: We saw that idiopathic DOR was the most common etiology. AMH titres are reflection of oocyte yield. Stop agonist-antagonist and micro dose flare gives a higher oocyte yield. More number of good quality blastocyst was available in antagonist cycles. Growth hormone as adjuvant is helpful in DOR cases.

Conclusions: DOR needs special care and urgency in treatment. Appropriate selection of protocol and adjuvants to treatment gives adequate pregnancy rate.


Diminished ovarian reserve, Stimulation protocol, Stop-antagonist protocol

Full Text:



Greene AD, Patounakis G, Segars JH. Genetic associations with diminished ovarian reserve: a systematic review of the literature. J Assist Reprod Genet. 2014;31(8):935-46.

Speroff L. The effect of aging on fertility. Curr Opin Obstet Gynecol. 1994;6(2):115-20.

Xiao J, Song J, Sa Y, Yuan L, Guo J, Sun Z. The Mechanisms of improving IVF outcomes of liu-wei-di-huang pill acting on DOR patients. Evid Based Complement Alternat Med. 2020;2020:5183017.

Bercaire L, Nogueira SM, Lima PC, Alves VR, Donadio N, Dzik A, et al. ANDRO-IVF: a novel protocol for poor responders to IVF controlled ovarian stimulation. JBRA Assist Reprod. 2018;22(1):52-5.

Tal R, Seifer DB. Ovarian reserve testing: a user's guide. Am J Obstet Gynecol. 2017;217(2):129-40.

Kawwass JF, Hipp HS, Session DR, Kissin DM, Jamieson DJ, National ART surveillance system group. severity of diminished ovarian reserve and chance of success with assisted reproductive technology. J Reprod Med. 2017;62(3-4):153-60.

Yun BH, Kim G, Park SH, Noe EB, Seo SK, Cho S, et al. In vitro fertilization outcome in women with diminished ovarian reserve. Obstet Gynecol Sci. 2017;60(1):46-52.

Bedenk J, Vrtacnik BE, Virant KI. The role of anti-Mullerian hormone (AMH) in ovarian disease and infertility. J Assist Reprod Genet. 2020;37(1):89-100.

Usta T, Oral E. Is the measurement of anti-Müllerian hormone essential?. Curr Opin Obstet Gynecol. 2012;24(3):151-7.

Wang S, Zhang Y, Mensah V, Huber WJ, Huang YT, Alvero R. Discordant anti-müllerian hormone (AMH) and follicle stimulating hormone (FSH) among women undergoing in vitro fertilization (IVF): which one is the better predictor for live birth? J Ovarian Res. 2018;11(1):60.

Lehmann P, Velez MP, Saumet J, Lapensee L, Jamal W, Bissonnette F, et al. Anti-Müllerian hormone (AMH): a reliable biomarker of oocyte quality in IVF. J Assist Reprod Genet. 2014;31(4):493-8.

Chang Y, Li J, Li X, Liu H, Liang X. Egg Quality and Pregnancy Outcome in Young Infertile Women with Diminished Ovarian Reserve. Med Sci Monit. 2018;24:7279-84.

Vollenhoven B, Hunt S. Ovarian ageing and the impact on female fertility. F1000Res. 2018;7:1000.

González-Foruria I, Peñarrubia J, Borràs A, Manau D, Casals G, Peralta S, et al. Age, independent from ovarian reserve status, is the main prognostic factor in natural cycle in vitro fertilization. Fertil Steril. 2016;106(2):342-7.

American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and Practice Committee. Female age-related fertility decline. Committee Opinion No. 589. Fertil Steril. 2014;101(3):633-4.

Ferraretti AP, Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L, et al. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26(7):1616-24.

Ozelçi R, Aldemir O, Dilbaz S, Ozkaya E, Kahyaoglu I, Dilbaz B, Moraloglu TO. The impact of different etiologies of diminished ovarian reserve on pregnancy outcome in IVF-ET cycles. Turk J Med Sci. 2019;49(4):1138-44.

Yun BH, Kim G, Park SH, Noe EB, Seo SK, Cho S, Choi YS, et al. In vitro fertilization outcome in women with diminished ovarian reserve. Obstet Gynecol Sci. 2017;60(1):46-52.

Guler I, Erdem A, Oguz Y, Cevher F, Mutlu MF, Bozkurt N, Oktem M, et al. The Impact of laparoscopic surgery of peritoneal endometriosis and endometrioma on the outcome of ICSI cycles. Syst Biol Reprod Med. 2017;63(5):324-30.

Haahr T, Esteves SC, Humaidan P. Individualized controlled ovarian stimulation in expected poor-responders: an update. Reprod Biol Endocrinol. 2018;16(1):20.

Zhao F, Lan Y, Chen T, Xin Z, Liang Y, Li Y, et al. Live birth rate comparison of three controlled ovarian stimulation protocols for in vitro fertilization-embryo transfer in patients with diminished ovarian reserve after endometrioma cystectomy: a retrospective study. J Ovarian Res. 2020;13(1):23.

Huang MC, Tzeng SL, Lee CI, Chen HH, Huang CC, Lee TH, et al. GnRH agonist long protocol versus GnRH antagonist protocol for various aged patients with diminished ovarian reserve: A retrospective study. PLoS One. 2018;13(11):207081.

Yu R, Jin H, Huang X, Lin J, Wang P. Comparison of modified agonist, mild-stimulation and antagonist protocols for in vitro fertilization in patients with diminished ovarian reserve. J Int Med Res. 2018;46(6):2327-37.

Jing M, Lin C, Zhu W, Tu X, Chen Q, Wang X, et al. Cost-effectiveness analysis of GnRH-agonist long-protocol and GnRH-antagonist protocol for in vitro fertilization. Sci Rep. 2020;10(1):8732.

Toftager M, Sylvest R, Schmidt L, Bogstad J, Lossl K, Pratorius L, et al. Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols. Fertil Steril. 2018;109(1):154-64.

Orvieto R, Nahum R, Aizer A, Haas J, Kirshenbaum M. A Novel Stimulation Protocol for Poor-Responder Patients: Combining the Stop GnRH-ag Protocol with Letrozole Priming and Multiple-Dose GnRH-ant: A Proof of Concept. Gynecol Obstet Invest. 2021;86(1):149-54.

Davar R, Neghab N, Naghshineh E. Pregnancy outcome in delayed start antagonist versus microdose flare GnRH agonist protocol in poor responders undergoing IVF/ICSI: An RCT. Int J Reprod Biomed. 2018;16(4):255-60.

Bercaire L, Nogueira SM, Lima PC, Alves VR, Donadio N, Dzik A, et al. ANDRO-IVF: a novel protocol for poor responders to IVF controlled ovarian stimulation. JBRA Assist Reprod. 2018;22(1):52-5.

Lu Q, Shen H, Li Y, Zhang C, Wang C, Chen X, Liang R, et al. Low testosterone levels in women with diminished ovarian reserve impair embryo implantation rate: a retrospective case-control study. J Assist Reprod Genet. 2014;31(4):485-91.

Ya Y, Kai W, Qiuping Y, Shen T, Kun L. Controlled ovarian stimulation protocols in endometriosis patients: with antagonist or agonist?. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2019;48(2):165-73.

Lin MH, Wu FS, Hwu YM, Lee RK, Li RS, Li SH. Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin significantly improves live birth rate for women with diminished ovarian reserve. Reprod Biol Endocrinol. 2019;17(1):7.

Chen SN, Tsui KH, Wang PH, Chern CU, Wen ZH, Lin LT. Dehydroepiandrosterone supplementation improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve. Front Endocrinol. 2019;10:800.

Triantafyllidou O, Sigalos G, Vlahos N. Dehydroepiandrosterone (DHEA) supplementation and IVF outcome in poor responders. Hum Fertil. 2017;20(2):80-7.

Moini A, Zafarani F, Jahangiri N, Jahanian Sadatmahalleh SH, Sadeghi M, Chehrazi M, et al. The effect of vaginal sildenafil on the outcome of assisted reproductive technology cycles in patients with repeated implantation failures: a randomized placebo-controlled trial. Int J Fertil Steril. 2020;13(4):289-95.

Gleicher N, Kim A, Michaeli T, Lee HJ, Shohat TA, Lazzaroni E, et al. A pilot cohort study of granulocyte colony-stimulating factor in the treatment of unresponsive thin endometrium resistant to standard therapies. Hum Reprod. 2013;28(1):172-7.

Xu YM, Hao GM, Gao BL. Application of growth hormone in in vitro fertilization. Front Endocrinol. 2019;10:502.

Lee YX, Shen MS, Tzeng CR. Low dose growth hormone adjuvant treatment with ultra-long ovarian stimulation protocol in poor responders showed non-inferior pregnancy outcome compared with normal responders. Front Endocrinol. 2019;10:892.

Guan Q, Ma HG, Wang YY, Zhang F. Effects of co-administration of growth hormone (GH) and aspirin to women during in vitro fertilization and embryo transfer (IVF-ET) cycles. Zhonghua Nan Ke Xue. 2007;13(9):798-800.

Yu CM, Dai XL, Wang YF, Gao TT, Cao F, Xia XY, et al. Progestin-primed ovarian stimulation improves the outcomes of IVF/ICSI cycles in infertile women with diminished ovarian reserve. J Chin Med Assoc. 2019;82(11):845-8.

Alviggi C, Conforti A, Esteves SC, Andersen CY, Bosch E, Buhler K, et al. Recombinant luteinizing hormone supplementation in assisted reproductive technology: a systematic review. Fertil Steril. 2018;109(4):644-64.