Optimizing Female Infertility in Premature Ovarian Insufficiency

Abstract

Premature ovarian failure is a complex pathology with numerous etiologies and multiple system sequelae resulting for early deprivation of ovarian sex hormones. In the studies to determine the etiology, it is seen that many patients are in the unexplained group. On the other hand, genetic predisposition and autoimmune cause of premature ovarian insufficiency (POI) are the most common known etiologic causes. Early diagnosis and energetic treatment are important in order to prevent symptoms related to estrogen deficiency. Initiating hormone replacement therapy as soon as possible will prevent menopausal symptoms and reduce long-term complications in women. Another important problem in these patients is infertility, which occurs due to ovarian failure. In fact, fertility, which begins to decrease before menstrual irregularity, turns into infertility with a rapid decline in the number of follicles in the following period. Here, the detection of patients at risk and appropriately timed fertility preservation treatments (such as freezing of oocyte, embryo, or ovarian tissue) or assisted reproductive techniques can be offered. Besides this, studies like stem cell therapy, platelet-rich plasma (PRP), and in vitro activation of ovarian tissue in patients with POI are recent and still investigational but may be promising in the future. In the present review, the current pathophysiology and treatment options of premature ovarian failure were discussed.

Keywords

• Premature ovarian insufficiency
• infertility
• diagnosis
• treatment

Erken Yumurtalık Yetersizliğinde Kadın İnfertilitesinin Optimizasyonu

Abstract

Erken yumurtalık yetmezliği, az bilinen etiyolojisi ile neden olduğu yumurtalık hormonlarının azalmasıyla saptanan, kadınlarda birçok sistemi etkileyen patolojilere yol açar. Etiyolojisini belirlemeye yönelik çalışmalarda pek çok hastanın açıklanamayan grupta olduğu görülmektedir. Diğer yandan genetik yatkınlık ve otoimmün nedenli erken yumurtalık yetersizliği (premature ovarian insufficiency, POI) bilinen en sık etiyolojik nedenlerdir. Temelde östrojen eksikliği ile ilgili semptomların önlenmesi amacı ile erken tanı ve tedavi önemlidir. Hormon replasman tedavisinin bir an önce başlanması, kadınlarda menopozal semptomların önlenmesini ve uzun dönemli komplikasyonların azalmasını sağlayacaktır. Bu hastalarda diğer önemli sorun ise over yetmezliği ile ortaya çıkan infertilitedir. Aslında adet düzensizliği ortaya çıkmadan önce azalmaya başlayan fertilite, ilerleyen dönemde folikül sayısının daha hızlı azalması ile ciddi bir infertilite sorunu haline gelmektedir. Burada özellikle risk altındaki hastaların tespiti ile uygun zamanda fertilite koruyucu tedaviler (oosit, embryo veya over dokusunun dondurulması gibi) ve yardımla üreme teknikleri önerilebilir. Bununla birlikte, infertilite yakınması olan POI tanısı alan hastalarda; kök hücre tedavisi, trombositten zengin plazma (platelet-rich plasma, PRP) ve over dokusuna in vitro aktivasyon gibi uygulamalar yeni ve deneysel aşamada olsa da gelecekte umut verici olabilir. Sunulan bu derlemede erken yumurtalık yetmezliğinin güncel patofizyolojisi ve tedavi seçenekleri tartışılmıştır.

Keywords

• Erken yumurtalık yetersizliği
• infertilite
• tanı
• tedavi

References

1. Webber L, Davies M, Anderson R, Bartlett J, Braat D, Cartwright B, et al. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926-37.
2. Golezar S, Ramezani Tehrani F, Khazaei S, Ebadi A, Keshavarz Z. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis. Climacteric. 2019;22(4):403-11.
3. Hubayter ZR, Popat V, Vanderhoof VH, Ndubizu O, Johnson D, Mao E, et al. A prospective evaluation of antral follicle function in women with 46,XX spontaneous primary ovarian insufficiency. Fertil Steril. 2010;94(5):1769-74.
4. van Kasteren YM, Schoemaker J. Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum Reprod Update. 1999;5(5):483-92.
5. Maclaran K, Panay N. Current concepts in premature ovarian insufficiency. Womens Health (Lond). 2015;11(2):169-82.
6. Luborsky JL, Meyer P, Sowers MF, Gold EB, Santoro N. Premature menopause in a multi-ethnic population study of the menopause transition. Hum Reprod. 2003;18(1):199-206.
7. Chang SH, Kim CS, Lee KS, Kim H, Yim SV, Lim YJ, et al. Premenopausal factors influencing premature ovarian failure and early menopause. Maturitas. 2007;58(1):19-30.
8. Turkyilmaz A, Alavanda C, Ates EA, Geckinli BB, Polat H, Gokcu M, et al. Whole-exome sequencing reveals new potential genes and variants in patients with premature ovarian insufficiency. J Assist Reprod Genet. 2022;39(3):695-710.

9. Lambrinoudaki I, Paschou SA, Lumsden MA, Faubion S, Makrakis E, Kalantaridou S, et al. Premature ovarian insufficiency: A toolkit for the primary care physician. Maturitas. 2021;147:53-63.
10. Tartagni M, Cicinelli E, De Pergola G, De Salvia MA, Lavopa C, Loverro G. Effects of pretreatment with estrogens on ovarian stimulation with gonadotropins in women with premature ovarian failure: a randomized, placebo-controlled trial. Fertil Steril. 2007;87(4):858-61.
11. Badawy A, Goda H, Ragab A. Induction of ovulation in idiopathic premature ovarian failure: a randomized double-blind trial. Reprod Biomed Online. 2007;15(2):215-9.
12. Check JH, Nowroozi K, Chase JS, Nazari A, Shapse D, Vaze M. Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea. Fertil Steril. 1990;53(5):811-6.
13. Ishizuka B, Furuya M, Kimura M, Kamioka E, Kawamura K. Live birth rate in patients with premature ovarian insufficiency during long-term follow-up under hormone replacement with or without ovarian stimulation. Front Endocrinol (Lausanne). 2021;12:795724.
14. Grin L, Ishizuka B, Onimaru A, Furuya M, Kawamura K. Impact of abnormal karyotype on reproductive outcome in premature ovarian insufficiency. Reprod Med Biol. 2022;21(1):e12471.
15. Jiao X, Meng T, Zhai Y, Zhao L, Luo W, Liu P, et al. Ovarian reserve markers in premature ovarian insufficiency: within different clinical stages and different etiologies. Front Endocrinol (Lausanne). 2021;12:601752.
16. Wong QHY, Yeung TWY, Yung SSF, Ko JKY, Li HWR, Ng EHY. The effect of 12-month dehydroepiandrosterone supplementation on the menstrual pattern, ovarian reserve markers, and safety profile in women with premature ovarian insufficiency. J Assist Reprod Genet. 2018;35(5):857-62.
17. Qin JC, Fan L, Qin AP. The effect of dehydroepiandrosterone (DHEA) supplementation on women with diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis. J Gynecol Obstet Hum Reprod. 2017;46(1):1-7.
18. Gleicher N, Weghofer A, Barad DH. Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation. Reprod Biomed Online. 2010;21(3):360-5.
19. Mamas L, Mamas E. Premature ovarian failure and dehydroepiandrosterone. Fertil Steril. 2009;91(2):644-6.
20. Mamas L, Mamas E. Dehydroepiandrosterone supplementation in assisted reproduction: rationale and results. Curr Opin Obstet Gynecol. 2009;21(4):306-8.
21. Sönmezer M, Ozmen B, Cil AP, Ozkavukçu S, Taşçi T, Olmuş H, et al. Dehydroepiandrosterone supplementation improves ovarian response and cycle outcome in poor responders. Reprod Biomed Online. 2009;19(4):508-13.
22. Hoang QH, Ho HS, Do HT, Nguyen TV, Nguyen HP, Le MT. Therapeutic effect of prolonged testosterone pretreatment in women with poor ovarian response: A randomized control trial. Reprod Med Biol. 2021;20(3):305-12.
23. Kim CH, Ahn JW, Moon JW, Kim SH, Chae HD, Kang BM. Ovarian features after 2 weeks, 3 weeks and 4 weeks transdermal testosterone gel treatment and their associated effect on IVF outcomes in poor responders. Dev Reprod. 2014;18(3):145-52.
24. Doan HT, Quan LH, Nguyen TT. The effectiveness of transdermal testosterone gel 1% (androgel) for poor responders undergoing in vitro fertilization. Gynecol Endocrinol. 2017;33(12):977-79.
25. Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, et al. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci USA. 2013;110(43):17474-9.
26. Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, et al. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015;30(3):608-15.
27. Hsueh AJW, Kawamura K. Hippo signaling disruption and ovarian follicle activation in infertile patients. Fertil Steril. 2020;114(3):458-64.
28. Hosseini L, Shirazi A, Naderi MM, Shams-Esfandabadi N, Borjian Boroujeni S, Sarvari A, et al. Platelet-rich plasma promotes the development of isolated human primordial and primary follicles to the preantral stage. Reprod Biomed Online. 2017;35(4):343-50.
29. Cakiroglu Y, Saltik A, Yuceturk A, Karaosmanoglu O, Kopuk SY, Scott RT, et al. Effects of intraovarian injection of autologous platelet rich plasma on ovarian reserve and IVF outcome parameters in women with primary ovarian insufficiency. Aging (Albany NY). 2020;12(11):10211-22.
30. Barad DH, Albertini DF, Molinari E, Gleicher N. Preliminary report of intraovarian injections of autologous platelet-rich plasma (PRP) in extremely poor prognosis patients with only oocyte donation as alternative: a prospective cohort study. Hum Reprod Open. 2022;2022(3):hoac027.
31. Cakiroglu Y, Yuceturk A, Karaosmanoglu O, Kopuk SY, Korun ZEU, Herlihy N, et al. Ovarian reserve parameters and IVF outcomes in 510 women with poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP). Aging (Albany NY). 2022;14(6):2513-23.
32. Herraiz S, Romeu M, Buigues A, Martínez S, Díaz-García C, Gómez-Seguí I, et al. Autologous stem cell ovarian transplantation to increase reproductive potential in patients who are poor responders. Fertil Steril. 2018;110(3):496-505.e1.
33. Wang J, Liu W, Yu D, Yang Z, Li S, Sun X. Research progress on the treatment of premature ovarian failure using mesenchymal stem cells: a literature review. Front Cell Dev Biol. 2021;9:749822.
34. Practice Committee of the American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2019;112(6):1022-33.