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Published in: Journal of Assisted Reproduction and Genetics 11/2019

01-11-2019 | Infertility | Reproductive Physiology and Disease

Impact of hypogonadotropic hypogonadism on ovarian reserve and response

Authors: Gustavo N. Cecchino, Guillermo M. Canillas, María Cruz, Juan A. García-Velasco

Published in: Journal of Assisted Reproduction and Genetics | Issue 11/2019

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Abstract

Objective

To evaluate the hormonal profile, antral follicle count (AFC) and ovarian response of patients with hypogonadotropic hypogonadism (HH).

Design

Observational retrospective cohort including infertile women with HH undergoing assisted reproductive treatment (ART).

Setting

University-affiliated infertility center.

Patient(s)

Thirty-three women with HH who underwent ART between January 2007 and September 2018. The control group comprised 66 age-matched counterparts with tubal or male factor infertility. The patients with an abnormal karyotype, and those presenting primary or secondary amenorrhea due to other causes, were cautiously excluded.

Intervention(s)

None.

Main outcome measure(s)

The primary outcome was serum levels of anti-Müllerian hormone (AMH) and AFC. We also investigated whether HH impacts ovarian response and reproductive outcomes.

Result(s)

Although AFC was similar between groups, HH patients showed significantly higher AMH levels (4.6 ± 2.7 ng/mL vs. 3.0 ± 1.9, p = 0.010) and lower basal FSH and LH. While the HH group needed longer stimulation [13 days (11–26) vs. 10 (7–14), p < 0.001] and higher gonadotropin doses [2700 IU (825–6300) vs. 2100 (425–5000), p = 0.038 ], no significant differences were detected in either the number or maturity of retrieved oocytes, or in the fertilization rate, number of embryos transferred, implantation rate, clinical pregnancy rate and live birth rate per cycle.

Conclusion(s)

HH patients present higher AMH levels, but similar AFC. Despite requiring longer stimulation and higher gonadotropin doses, ovarian response and reproductive outcomes seem unaffected.
Literature
1.
go back to reference Boehm U, Bouloux P-M, Dattani MT, de Roux N, Dodé C, Dunkel L, et al. European consensus statement on congenital hypogonadotropic hypogonadism —pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11:547–64.CrossRef Boehm U, Bouloux P-M, Dattani MT, de Roux N, Dodé C, Dunkel L, et al. European consensus statement on congenital hypogonadotropic hypogonadism —pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11:547–64.CrossRef
2.
go back to reference Silveira LFG, Latronico AC. Approach to the patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013;98:1781–8.CrossRef Silveira LFG, Latronico AC. Approach to the patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013;98:1781–8.CrossRef
3.
go back to reference Jonard S, Pigny P, Jacquesson L, Demerle-Roux C, Robert Y, Dewailly D. The ovarian markers of the FSH insufficiency in functional hypothalamic amenorrhoea. Hum Reprod. 2005;20:101–7.CrossRef Jonard S, Pigny P, Jacquesson L, Demerle-Roux C, Robert Y, Dewailly D. The ovarian markers of the FSH insufficiency in functional hypothalamic amenorrhoea. Hum Reprod. 2005;20:101–7.CrossRef
4.
go back to reference Tal R, Seifer DB. Ovarian reserve testing: a user’s guide. Am J Obstet Gynecol. 2017;217:129–40.CrossRef Tal R, Seifer DB. Ovarian reserve testing: a user’s guide. Am J Obstet Gynecol. 2017;217:129–40.CrossRef
5.
go back to reference Fanchin R, Schonäuer LM, Righini C, Guibourdenche J, Frydman R, Taieb J. Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum Reprod. 2003;18:323–7.CrossRef Fanchin R, Schonäuer LM, Righini C, Guibourdenche J, Frydman R, Taieb J. Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum Reprod. 2003;18:323–7.CrossRef
6.
go back to reference Gao Y, Yu B, Mao J, Wang X, Nie M, Wu X. Assisted reproductive techniques with congenital hypogonadotropic hypogonadism patients: a systematic review and meta-analysis. BMC Endocr Disord. 2018;18:85.CrossRef Gao Y, Yu B, Mao J, Wang X, Nie M, Wu X. Assisted reproductive techniques with congenital hypogonadotropic hypogonadism patients: a systematic review and meta-analysis. BMC Endocr Disord. 2018;18:85.CrossRef
7.
go back to reference Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, et al. Elevated serum level of anti-Mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab. 2003;88:5957–62.CrossRef Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, et al. Elevated serum level of anti-Mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab. 2003;88:5957–62.CrossRef
8.
go back to reference Baarends WM, Uilenbroek JT, Kramer P, Hoogerbrugge JW, van Leeuwen EC, Themmen AP, et al. Anti-müllerian hormone and anti-müllerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth. Endocrinology. 1995;136:4951–62.CrossRef Baarends WM, Uilenbroek JT, Kramer P, Hoogerbrugge JW, van Leeuwen EC, Themmen AP, et al. Anti-müllerian hormone and anti-müllerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth. Endocrinology. 1995;136:4951–62.CrossRef
9.
go back to reference Yilmaz S, Ozgu-Erdinc AS, Yumusak O, Kahyaoglu S, Seckin B, Yilmaz N. The reproductive outcome of women with hypogonadotropic hypogonadism undergoing in vitro fertilization. Syst Biol Reprod Med. 2015;61:228–32.CrossRef Yilmaz S, Ozgu-Erdinc AS, Yumusak O, Kahyaoglu S, Seckin B, Yilmaz N. The reproductive outcome of women with hypogonadotropic hypogonadism undergoing in vitro fertilization. Syst Biol Reprod Med. 2015;61:228–32.CrossRef
10.
go back to reference 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;37:120–2.PubMed 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;37:120–2.PubMed
11.
go back to reference Ulug U, Ben-Shlomo I, Tosun S, Erden HF, Akman MA, Bahceci M. The reproductive performance of women with hypogonadotropic hypogonadism in an in vitro fertilization and embryo transfer program. J Assist Reprod Genet. 2005;22:167–71.CrossRef Ulug U, Ben-Shlomo I, Tosun S, Erden HF, Akman MA, Bahceci M. The reproductive performance of women with hypogonadotropic hypogonadism in an in vitro fertilization and embryo transfer program. J Assist Reprod Genet. 2005;22:167–71.CrossRef
12.
go back to reference Jiang S, Kuang Y. The effects of low-dose human chorionic gonadotropin combined with human menopausal gonadotropin protocol on women with hypogonadotropic hypogonadism undergoing ovarian stimulation for in vitro fertilization. Clin Endocrinol. 2018;88:77–87.CrossRef Jiang S, Kuang Y. The effects of low-dose human chorionic gonadotropin combined with human menopausal gonadotropin protocol on women with hypogonadotropic hypogonadism undergoing ovarian stimulation for in vitro fertilization. Clin Endocrinol. 2018;88:77–87.CrossRef
13.
go back to reference Labarta E, Mariani G, Holtmann N, Celada P, Remohí J, Bosch E. Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Hum Reprod. 2017;32:2437–42.CrossRef Labarta E, Mariani G, Holtmann N, Celada P, Remohí J, Bosch E. Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Hum Reprod. 2017;32:2437–42.CrossRef
14.
go back to reference Bry-Gauillard H, Larrat-Ledoux F, Levaillant J-M, Massin N, Maione L, Beau I, et al. Anti-Müllerian hormone and ovarian morphology in women with isolated hypogonadotropic hypogonadism/Kallmann syndrome: effects of recombinant human FSH. J Clin Endocrinol Metab. 2017;102:1102–11.CrossRef Bry-Gauillard H, Larrat-Ledoux F, Levaillant J-M, Massin N, Maione L, Beau I, et al. Anti-Müllerian hormone and ovarian morphology in women with isolated hypogonadotropic hypogonadism/Kallmann syndrome: effects of recombinant human FSH. J Clin Endocrinol Metab. 2017;102:1102–11.CrossRef
15.
go back to reference Tsilchorozidou T, Conway GS. Uterus size and ovarian morphology in women with isolated growth hormone deficiency, hypogonadotrophic hypogonadism and hypopituitarism. Clin Endocrinol. 2004;61:567–72.CrossRef Tsilchorozidou T, Conway GS. Uterus size and ovarian morphology in women with isolated growth hormone deficiency, hypogonadotrophic hypogonadism and hypopituitarism. Clin Endocrinol. 2004;61:567–72.CrossRef
16.
go back to reference Couzinet B, Young J, Brailly S, Le Bouc Y, Chanson P, Schaison G. Functional hypothalamic amenorrhoea: a partial and reversible gonadotrophin deficiency of nutritional origin. Clin Endocrinol. 1999;50:229–35.CrossRef Couzinet B, Young J, Brailly S, Le Bouc Y, Chanson P, Schaison G. Functional hypothalamic amenorrhoea: a partial and reversible gonadotrophin deficiency of nutritional origin. Clin Endocrinol. 1999;50:229–35.CrossRef
17.
go back to reference Treasure JL, Wheeler M, King EA, Gordon PA, Russell GF. Weight gain and reproductive function: ultrasonographic and endocrine features in anorexia nervosa. Clin Endocrinol. 1988;29:607–16.CrossRef Treasure JL, Wheeler M, King EA, Gordon PA, Russell GF. Weight gain and reproductive function: ultrasonographic and endocrine features in anorexia nervosa. Clin Endocrinol. 1988;29:607–16.CrossRef
18.
go back to reference Futterweit W, Yeh HC, Mechanick JI. Ultrasonographic study of ovaries of 19 women with weight loss-related hypothalamic oligo-amenorrhea. Biomed Pharmacother. 1988;42:279–83.PubMed Futterweit W, Yeh HC, Mechanick JI. Ultrasonographic study of ovaries of 19 women with weight loss-related hypothalamic oligo-amenorrhea. Biomed Pharmacother. 1988;42:279–83.PubMed
19.
go back to reference Shoham Z, Conway GS, Patel A, Jacobs HS. Polycystic ovaries in patients with hypogonadotropic hypogonadism: similarity of ovarian response to gonadotropin stimulation in patients with polycystic ovarian syndrome. Fertil Steril. 1992;58:37–45.CrossRef Shoham Z, Conway GS, Patel A, Jacobs HS. Polycystic ovaries in patients with hypogonadotropic hypogonadism: similarity of ovarian response to gonadotropin stimulation in patients with polycystic ovarian syndrome. Fertil Steril. 1992;58:37–45.CrossRef
20.
go back to reference Wang JG, Lobo RA. The complex relationship between hypothalamic amenorrhea and polycystic ovary syndrome. J Clin Endocrinol Metab. 2008;93:1394–7.CrossRef Wang JG, Lobo RA. The complex relationship between hypothalamic amenorrhea and polycystic ovary syndrome. J Clin Endocrinol Metab. 2008;93:1394–7.CrossRef
21.
go back to reference Carmina E, Fruzzetti F, Lobo RA. Features of polycystic ovary syndrome (PCOS) in women with functional hypothalamic amenorrhea (FHA) may be reversible with recovery of menstrual function. Gynecol Endocrinol. 2018;34:301–4.CrossRef Carmina E, Fruzzetti F, Lobo RA. Features of polycystic ovary syndrome (PCOS) in women with functional hypothalamic amenorrhea (FHA) may be reversible with recovery of menstrual function. Gynecol Endocrinol. 2018;34:301–4.CrossRef
22.
go back to reference Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17:121–55.CrossRef Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17:121–55.CrossRef
23.
go back to reference Couzinet B, Lestrat N, Brailly S, Forest M, Schaison G. Stimulation of ovarian follicular maturation with pure follicle-stimulating hormone in women with gonadotropin deficiency. J Clin Endocrinol Metab. 1988;66:552–6.CrossRef Couzinet B, Lestrat N, Brailly S, Forest M, Schaison G. Stimulation of ovarian follicular maturation with pure follicle-stimulating hormone in women with gonadotropin deficiency. J Clin Endocrinol Metab. 1988;66:552–6.CrossRef
24.
go back to reference Shoham Z, Smith H, Yeko T, O’Brien F, Hemsey G, O’Dea L. Recombinant LH (lutropin alfa) for the treatment of hypogonadotrophic women with profound LH deficiency: a randomized, double-blind, placebo-controlled, proof-of-efficacy study. Clin Endocrinol. 2008;69:471–8.CrossRef Shoham Z, Smith H, Yeko T, O’Brien F, Hemsey G, O’Dea L. Recombinant LH (lutropin alfa) for the treatment of hypogonadotrophic women with profound LH deficiency: a randomized, double-blind, placebo-controlled, proof-of-efficacy study. Clin Endocrinol. 2008;69:471–8.CrossRef
25.
go back to reference Kaufmann R, Dunn R, Vaughn T, Hughes G, O’Brien F, Hemsey G, et al. Recombinant human luteinizing hormone, lutropin alfa, for the induction of follicular development and pregnancy in profoundly gonadotrophin-deficient women. Clin Endocrinol. 2007;64:563–9. Kaufmann R, Dunn R, Vaughn T, Hughes G, O’Brien F, Hemsey G, et al. Recombinant human luteinizing hormone, lutropin alfa, for the induction of follicular development and pregnancy in profoundly gonadotrophin-deficient women. Clin Endocrinol. 2007;64:563–9.
26.
go back to reference Filicori M, Cognigni GE, Pocognoli P, Tabarelli C, Ferlini F, Perri T, et al. Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle-stimulating hormone. Fertil Steril. 2003;80:390–7.CrossRef Filicori M, Cognigni GE, Pocognoli P, Tabarelli C, Ferlini F, Perri T, et al. Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle-stimulating hormone. Fertil Steril. 2003;80:390–7.CrossRef
27.
go back to reference Kumbak B, Kahraman S. Women with hypogonadotropic hypogonadism: cycle characteristics and results of assisted reproductive techniques. Acta Obstet Gynecol Scand. 2006;85:1453–7.CrossRef Kumbak B, Kahraman S. Women with hypogonadotropic hypogonadism: cycle characteristics and results of assisted reproductive techniques. Acta Obstet Gynecol Scand. 2006;85:1453–7.CrossRef
28.
go back to reference Lewit N, Kol S. The low responder female IVF patient with hypogonadotropic hypogonadism: do not give up! Fertil Steril. 2000;74:401–2.CrossRef Lewit N, Kol S. The low responder female IVF patient with hypogonadotropic hypogonadism: do not give up! Fertil Steril. 2000;74:401–2.CrossRef
29.
go back to reference Balasch J, Miró F, Burzaco I, Casamitjana R, Civico S, Ballescá JL, et al. The role of luteinizing hormone in human follicle development and oocyte fertility: evidence from in-vitro fertilization in a woman with long-standing hypogonadotrophic hypogonadism and using recombinant human follicle stimulating hormone. Hum Reprod. 1995;10:1678–83.CrossRef Balasch J, Miró F, Burzaco I, Casamitjana R, Civico S, Ballescá JL, et al. The role of luteinizing hormone in human follicle development and oocyte fertility: evidence from in-vitro fertilization in a woman with long-standing hypogonadotrophic hypogonadism and using recombinant human follicle stimulating hormone. Hum Reprod. 1995;10:1678–83.CrossRef
30.
go back to reference Rama Raju G, Chavan R, Deenadayal M, Govindarajan M, Gunasheela D, Gutgutia R, et al. Luteinizing hormone and follicle stimulating hormone synergy: a review of role in controlled ovarian hyper-stimulation. J Hum Reprod Sci. 2013;6:227.CrossRef Rama Raju G, Chavan R, Deenadayal M, Govindarajan M, Gunasheela D, Gutgutia R, et al. Luteinizing hormone and follicle stimulating hormone synergy: a review of role in controlled ovarian hyper-stimulation. J Hum Reprod Sci. 2013;6:227.CrossRef
31.
go back to reference The European Recombinant Human LH Study Group. Recombinant human luteinizing hormone (LH) to support recombinant human follicle-stimulating hormone (FSH)-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. J Clin Endocrinol Metab. 1998;83:1507–14. The European Recombinant Human LH Study Group. Recombinant human luteinizing hormone (LH) to support recombinant human follicle-stimulating hormone (FSH)-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. J Clin Endocrinol Metab. 1998;83:1507–14.
32.
go back to reference Practice Committee of American Society for Reproductive Medicine. Use of exogenous gonadotropins in anovulatory women: a technical bulletin. Fertil Steril. 2008;90:S7–12. Practice Committee of American Society for Reproductive Medicine. Use of exogenous gonadotropins in anovulatory women: a technical bulletin. Fertil Steril. 2008;90:S7–12.
33.
go back to reference Castillo JC, Garcia-Velasco J, Humaidan P. Empty follicle syndrome after GnRHa triggering versus hCG triggering in COS. J Assist Reprod Genet. 2012;29:249–53.CrossRef Castillo JC, Garcia-Velasco J, Humaidan P. Empty follicle syndrome after GnRHa triggering versus hCG triggering in COS. J Assist Reprod Genet. 2012;29:249–53.CrossRef
34.
go back to reference Mumusoglu S, Ata B, Turan V, Demir B, Kahyaoglu I, Aslan K, et al. Does pituitary suppression affect live birth rate in women with congenital hypogonadotrophic hypogonadism undergoing intra-cytoplasmic sperm injection? A multicenter cohort study. Gynecol Endocrinol. 2017;33:728–32.CrossRef Mumusoglu S, Ata B, Turan V, Demir B, Kahyaoglu I, Aslan K, et al. Does pituitary suppression affect live birth rate in women with congenital hypogonadotrophic hypogonadism undergoing intra-cytoplasmic sperm injection? A multicenter cohort study. Gynecol Endocrinol. 2017;33:728–32.CrossRef
Metadata
Title
Impact of hypogonadotropic hypogonadism on ovarian reserve and response
Authors
Gustavo N. Cecchino
Guillermo M. Canillas
María Cruz
Juan A. García-Velasco
Publication date
01-11-2019
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 11/2019
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-019-01587-7

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