Pregnancy Outcomes After Gonadotropin Ovulation Induction in Women with Hypogonadotropic Hypogonadism Compared with Those in Women with Unexplained Infertility

Öz

Objective: Hypogonadotropic hypogonadism (HH) represents an uncommon cause of anovulatory infertility, characterized by inadequate gonadotropin secretion or an impaired pituitary response to gonadotropin-releasing hormone (GnRH). The present study evaluated pregnancy outcomes following gonadotropin-induced ovulation in women with HH and compared these outcomes with those observed in women with unexplained infertility (UI), while also examining clinical variables associated with treatment success. Materials and Methods: This retrospective comparative study evaluated ovulation induction cycles in women with HH and in a comparison group of women with UI who were treated at a tertiary infertility center between 2010 and 2020. All patients underwent gonadotropin-based ovulation induction followed by intrauterine insemination. Treatment characteristics and reproductive outcomes were compared between groups, and clinical variables associated with achieving pregnancy and cycle cancellation were analyzed. Results: The two groups were comparable with respect to age, body mass index, total progressive motile sperm count, and infertility type (p>0.05). Women with HH required higher initial and total gonadotropin doses and had longer stimulation periods (p<0.001). The number of follicles ≥14 mm and the rate of cycle cancellation were also higher in the HH group (p<0.001). Despite these differences, pregnancy, term birth, and miscarriage rates per cycle were similar between groups (p>0.05). In logistic regression analysis, a greater number of follicles on the trigger day was associated with an increased likelihood of cycle cancellation (p<0.001), whereas greater endometrial thickness on the trigger day was associated with higher pregnancy rates (p<0.001). Conclusion: In women with HH undergoing gonadotropin-based OI, endometrial thickness appears to be an important factor associated with pregnancy. Compared with women with UI, women with HH required higher gonadotropin doses and had higher cycle cancellation rates, largely because of multifollicular development. Despite these differences, pregnancy outcomes were comparable between the HH and UI groups when ovulation was achieved. Keywords: Gonadotropin treatment, Hypogonadotropic hypogonadism, Ovulation induction, Pregnancy.

Anahtar Kelimeler

• hypogonadptropic hypogonadism
• ovulation induction
• pregnancy
• gonadotropim treatment

Hipogonadotropik Hipogonadizmi Olan Kadınlarda Gonadotropinle Ovulasyon İndüksiyonu ve İntrauterin İnseminasyon Sonrası Gebelik Sonuçlarının Açıklanamayan İnfertilite ile Karşılaştırılması

Öz

Amaç: Hipogonadotropik Hipogonadizm (HH), yetersiz gonadotropin salınımı veya gonadotropin salgılatıcı hormona (GnRH) bozulmuş hipofizer yanıt ile karakterize, nadir görülen bir anovulatuvar infertilite nedenidir. Bu çalışmada, HH’li kadınlarda gonadotropinle ovulasyon indüksiyonu sonrası gebelik sonuçlarının değerlendirilmesi ve bu sonuçların açıklanamayan infertilite (Aİ) tanılı kadınlarla karşılaştırılması amaçlandı. Ayrıca tedavi başarısı ile ilişkili klinik değişkenler incelendi. Gereç ve Yöntem: Bu retrospektif karşılaştırmalı çalışmada, 2010–2020 yılları arasında üçüncü basamak bir infertilite merkezinde HH tanısı ile tedavi edilen kadınların ovulasyon indüksiyonu siklusları, açıklanamayan infertilite tanılı kadınlardan oluşan bir karşılaştırma grubu ile değerlendirildi. Tüm hastalara gonadotropin bazlı ovulasyon indüksiyonu uygulanmış ve bunu intrauterin inseminasyon izlemiştir. Gruplar arasında tedavi özellikleri ve üreme sonuçları karşılaştırılmış; gebelik elde edilmesi ve siklus iptali ile ilişkili klinik değişkenler analiz edilmiştir. Bulgular: İki grup yaş, vücut kitle indeksi, total progresif motil sperm sayısı ve infertilite tipi açısından benzerdi (p>0,05). HH grubundaki kadınlarda başlangıç ve toplam gonadotropin dozları daha yüksek olup stimülasyon süresi daha uzundu (p<0,001). Ayrıca ≥14 mm folikül sayısı ve siklus iptal oranı HH grubunda anlamlı olarak daha yüksekti (p<0,001). Bu farklılıklara rağmen, siklus başına gebelik, term doğum ve düşük oranları gruplar arasında benzerdi (p>0,05). Lojistik regresyon analizinde, tetikleme gününde folikül sayısının artması siklus iptali olasılığını artırırken (p<0,001), tetikleme gününde endometrium kalınlığının artması gebelik oranları ile pozitif ilişkili bulundu (p<0,001). Sonuç: Hipogonadotropik Hipogonadizmi olan kadınlarda gonadotropinle ovulasyon indüksiyonu sırasında endometrium kalınlığı, gebelik elde edilmesi ile ilişkili önemli bir faktör olarak görünmektedir. Açıklanamayan infertilite tanılı kadınlarla karşılaştırıldığında, HH grubunda multifoliküler gelişime bağlı olarak daha yüksek gonadotropin gereksinimi ve daha yüksek siklus iptal oranları izlenmiştir. Bununla birlikte, ovulasyon sağlandığında HH ve Aİ grupları arasında gebelik sonuçları benzer bulunmuştur. Anahtar Kelimeler: Gebelik, Gonadotropin tedavisi, Hipogonadotropik Hipogonadizm, Ovulasyon indüksiyonu.

Anahtar Kelimeler

• Gebelik
• Gonadotropin tedavisi
• Hipogonadotropik Hipogonadizm
• Ovulasyon indüksiyonu.

Kaynakça

1. World Health Organisation Guideline Development Group for Infertility, Mburu G, Santesso N, Brignardello-Petersen R, et al. Recommendations from the WHO guideline for the prevention, diagnosis, and treatment of infertility. Hum Reprod. 2025.
2. Mburu G, Kiarie J, Allotey P. WHO guideline on infertility: an opportunity to reduce global health inequalities. Lancet Glob Health. 2026;14:e12–13.
3. Ma Y-J, Li M-Y, Song J-Y, Sun Z-G. Application of human menopausal gonadotropins in the treatment of idiopathic hypogonadotropic hypogonadism (IHH)-based infertility in females: A case report. Int Med Case Rep J. 2023;16:699–704.
4. Bonomi M, Vezzoli V, Krausz C, et al. Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH). Eur J Endocrinol. 2018;178:23–32.
5. Ilboudo A, Sagna Y, Dubreuil S, Touraine P, Courtillot C. Infertility with hypogonadotropic hypogonadism revealing a classic form of 21 hydroxylase deficiency in a 39 year-old man. Ann Endocrinol (Paris). 2022;83:267–268.
6. Yildirim G, Ficicioglu C, Attar R, Akcin O, Tecellioglu N. Comparision of reproductive outcome of the women with hypogonadotropic hypogonadism and tubal factor infertility. Clin Exp Obstet Gynecol. 2010;37:120–122.
7. Shiraishi K, Ohmi C, Matsuyama H. Patient-reported outcomes and biochemical alterations during hormonal therapy in men with hypogonadotropic hypogonadism who have finished infertility treatment. Endocr J. 2021;68:221–229.
8. Saremi A, Golnavaz M, Pooladi A, et al. Evaluation the success rate of treatment failure in patients with unexplained repeated IVF treatments immunization with lymphocytes (LIT) methods. Sarem Journal of Reproductive Medicine. 2019;3:9–12.

9. Permadi IW, Prasetyaji IW. Breaking the cycle of infertility with clomiphene citrate and letrozole for successful ovulation induction for obese women with PCOS. Maj Obstet Ginekol. 2025;33:44–52.
10. Ahmed AEAM, Elboghdady AA, Ahmed IMM. Patient criteria for successful induction of ovulation by clomiphene citrate in patients with polycystic ovary syndrome. Al-Azhar International Medical Journal. 2023;4.
11. Szabo G, Szigeti F J, Sipos M, Varbiro S, Gonda X. The role of psychological factors in the development and treatment of infertility. Neuropsychopharmacol Hung. 2023;25:123–130.
12. Shoham Z, Balen A, Patel A, Jacobs HS. Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients. Int J Gynaecol Obstet. 1992;38:335.
13. Milsom S, Duggan K, O’sullivan S, Ogilvie M, Gunn AJ. Treatment of infertility with hypogonadotropic hypogonadism: 10-year experience in Auckland, New Zealand. Aust N Z J Obstet Gynaecol. 2012;52:293–298.
14. Huseyin K, Berk B, Tolga K, Eser O, Ali G, Murat A. Management of ovulation induction and intrauterine insemination in infertile patients with hypogonadotropic hypogonadism. J Gynecol Obstet Hum Reprod. 2019;48:833–838.
15. Kumbak B, Kahraman S. Women with hypogonadotropic hypogonadism: cycle characteristics and results of assisted reproductive techniques. Acta Obstet Gynecol Scand. 2006;85:1453–1457.
16. Xu W, Li R, Qiao J. ART outcomes of patients in women with Isolated Hypogonadotropic Hypogonadism: a retrospective study in China. BMC Pregnancy Childbirth. 2023;23:255.
17. Dubourdieu S, Fréour T, Dessolle L, Barrière P. Prospective, randomized comparison between pulsatile GnRH therapy and combined gonadotropin (FSH + LH) treatment for ovulation induction in women with hypothalamic amenorrhea and underlying. Eur J Obstet Gynecol Reprod Biol. 2013 May;168(1):45-48.
18. Richter KS, Bugge KR, Bromer JG, Levy MJ. Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertil Steril. 2007;87:53–59.
19. Kasius A, Smit JG, Torrance HL, Eijkemans MJC, Mol BW, Opmeer BC, et al. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update. 2014;20:530–541.