妊娠合并自发性卵巢过度刺激综合征一例

doi:10.12280/gjszjk.20210541

摘要/Abstract

摘要：

卵巢过度刺激综合征是辅助生殖技术常见的并发症,通常在排卵后2周或2周以上发生。然而自发性卵巢过度刺激综合征极其罕见,一些病例报道表明,自发性卵巢过度刺激综合征的发生与卵泡刺激素受体突变、高人绒毛膜促性腺激素水平、高促甲状腺激素水平、促性腺激素垂体腺瘤等有关。现报告1例双胎妊娠合并自发性卵巢过度刺激综合征的病例,并进一步探讨自发性卵巢过度刺激综合征的可能病因、诊断和治疗原则。

关键词: 自发性卵巢过度刺激综合征, 妊娠,双胎, 病因, 排卵诱导, 生殖技术,辅助, 病例报告

Abstract:

Ovarian hyperstimulation syndrome is a common complication in assisted reproductive technology. It usually occurs after two weeks or more of induced ovulation. However, the spontaneous ovarian hyperstimulation syndrome (sOHSS) is extremely rare. Some clinical cases showed that the etiology of sOHSS was related to the mutations of follicle stimulating hormone receptor gene, the high level of human chorionic gonadotropin (hCG), the high level of thyroid-stimulating hormone (TSH), and gonadotropin pituitary adenoma. In this paper, we report a case of twin pregnancy complicated with sOHSS, and further study the possible etiology, diagnosis and treatment of sOHSS.

Key words: Spontaneous ovarian hyperstimulation syndrome, Pregnancy, twin, Etiology, Ovulation induction, Reproductive techniques, assisted, Case reports

周多, 李亨静, 路广美, 黄秋芳, 张毅. 妊娠合并自发性卵巢过度刺激综合征一例[J]. 国际生殖健康/计划生育, 2022, 41(4): 298-301.

ZHOU Duo, LI Heng-jing, LU Guang-mei, HUANG Qiu-fang, ZHANG Yi. A Case of Spontaneous Ovarian Hyperstimulation Syndrome in Pregnancy[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(4): 298-301.

图/表 2

参考文献 32

[1]	Kasum M, Oreskovic S, Jezek D. Spontaneous ovarian hyperstimulation syndrome[J]. Coll Antropol, 2013, 37(2):653-656. pmid: 23941020
[2]	Panagiotopoulou N, Byers H, Newman WG, et al. Spontaneous ovarian hyperstimulation syndrome: case report, pathophysiological classification and diagnostic algorithm[J]. Eur J Obstet Gynecol Reprod Biol, 2013, 169(2):143-148. doi: 10.1016/j.ejogrb.2013.03.004. doi: 10.1016/j.ejogrb.2013.03.004 pmid: 23561021
[3]	Ascoli M, Fanelli F, Segaloff DL. The lutropin/choriogonadotropin receptor,a 2002 perspective[J]. Endocr Rev, 2002, 23(2):141-174. doi: 10.1210/edrv.23.2.0462. doi: 10.1210/edrv.23.2.0462 pmid: 11943741
[4]	Rizk B. Symposium: Update on prediction and management of OHSS. Genetics of ovarian hyperstimulation syndrome[J]. Reprod Biomed Online, 2009, 19(1):14-27. doi: 10.1016/s1472-6483(10)60041-7. doi: 10.1016/s1472-6483(10)60041-7 URL
[5]	Smits G, Olatunbosun O, Delbaere A, et al. Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor[J]. N Engl J Med, 2003, 349(8):760-766. doi: 10.1056/NEJMoa030064. doi: 10.1056/NEJMoa030064 URL
[6]	Vasseur C, Rodien P, Beau I, et al. A chorionic gonadotrophin sensitive mutation in the follicle stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome[J]. N Engl J Med, 2003, 349(8):753-759. doi: 10.1056/NEJMoa030065. doi: 10.1056/NEJMoa030065 URL
[7]	Montanelli L, Delbaere A, Di Carlo C, et al. A mutation in the follicle stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome[J]. J Clin Endocrinol Metab, 2004, 89(4):1255-1258. doi: 10.1210/jc.2003-031910. doi: 10.1210/jc.2003-031910 URL
[8]	De Leener A, Montanelli L, Van Durme J, et al. Presence and absence of follicle stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiology[J]. J Clin Endocrinol Metab, 2006, 91(2):555-562. doi: 10.1210/j.2005-1580. doi: 10.1210/j.2005-1580 URL
[9]	De Leener A, Caltabiano G, Erkan S, et al. Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome[J]. Hum Mutat, 2008, 29(1):91-98. doi: 10.1002/humu.20604. doi: 10.1002/humu.20604 pmid: 17721928
[10]	Uchida S, Uchida H, Maruyama T, et al. Molecular analysis of a mutated FSH receptor detected in a patient with spontaneous ovarian hyperstimulation syndrome[J]. PLoS One, 2013, 8(9):e75478. doi: 10.1371/journal.pone.0075478. doi: 10.1371/journal.pone.0075478 URL
[11]	Chauhan AR, Prasad M, Chamariya S, et al. Novel FSH receptor mutation in a case of spontaneous ovarian hyperstimulation syndrome with successful pregnancy outcome[J]. J Hum Reprod Sci, 2015, 8(4):230-233. doi: 10.4103/0974-1208.170410. doi: 10.4103/0974-1208.170410 URL
[12]	Hugon-Rodin J, Sonigo C, Gompel A, et al. First mutation in the FSHR cytoplasmic tail identified in a non-pregnant woman with spontaneous ovarian hyperstimulation syndrome[J]. BMC Med Genet, 2017, 18(1):44. doi: 10.1186/s12881-017-0407-6. doi: 10.1186/s12881-017-0407-6 pmid: 28446136
[13]	Gil Navarro N, Garcia Grau E, Pina Pérez S, et al. Ovarian tortion and pontaneous ovarian hyperstimulation syndrome in a twin pregnancy: A case report[J]. Int J Surg Case Rep, 2017, 34:66-68. doi: 10.1016/j.ijscr.2017.03.014. doi: 10.1016/j.ijscr.2017.03.014 URL
[14]	Tsubokura H, Ikoma Y, Yokoe T, et al. Ovarian hyperstimulation syndrome following surgical removal of a complete hydatidiform mole: a case report[J]. J Med Case Rep, 2019, 13(1):292. doi: 10.1186/s13256-019-2181-x. doi: 10.1186/s13256-019-2181-x URL
[15]	Davies MJ, Fletcher TL, Cox Bauer CM, et al. Spontaneous Ovarian Hyperstimulation Syndrome in a Partial Molar Pregnancy With Early Onset Severe Pre-eclampsia at 15 Weeks Gestation[J]. Mil Med, 2020, 185(9/10):e1836-e1839. doi: 10.1093/milmed/usaa008. doi: 10.1093/milmed/usaa008
[16]	Wu X, Zhu J, Zhao A. Ovarian hyperstimulation syndrome in a spontaneous pregnancy with invasive mole[J]. J Obstet Gynaecol Res, 2015, 41(5):817-822. doi: 10.1111/jog.12606. doi: 10.1111/jog.12606 URL
[17]	De Lucia DR, Castaldo A, D′Agostino V, et al. Metastatic choriocarcinoma with hemorrhagic complications and spontaneous ovarian hyperstimulation syndrome: A case report[J]. Radiol Case Rep, 2021, 16(12):3868-3874. doi: 10.1016/j.radcr.2021.09.031. doi: 10.1016/j.radcr.2021.09.031 URL
[18]	Schubert RL, Narayan P, Puett D. Specificity of cognate ligand-receptor interactions: fusion proteins of human chorionic gonadotropin and the heptahelical receptors for human luteinizing hormone, thyroid-stimulating hormone, and follicle-stimulating hormone[J]. Endocrinology, 2003, 144(1):129-137. doi: 10.1210/en.2002-220829. doi: 10.1210/en.2002-220829 pmid: 12488338
[19]	Vischer HF, Granneman JC, Noordam MJ, et al. Ligand selectivity of gonadotropin receptors. Role of the beta-strands of extracellular leucine-rich repeats 3 and 6 of the human luteinizing hormone receptor[J]. J Biol Chem, 2003, 278(18):15505-15513. doi: 10.1074/jbc.M300634200. doi: 10.1074/jbc.M300634200 pmid: 12598521
[20]	Rajaram S, Bhaskaran S, Aggarwal P, et al. Spontaneous ovarian hyperstimulation mimicking ovarian neoplasm: A rare complication of hypothyroidism[J]. J Obstet Gynaecol, 2015, 35(5):532-533. doi: 10.3109/01443615.2014.968112. doi: 10.3109/01443615.2014.968112 pmid: 25383867
[21]	Kim SJ, Yoon JH, Kim HK, et al. Spontaneous ovarian hyperstimulation syndrome in a young female subject with a lingual thyroid and primary hypothyroidism[J]. Korean J Intern Med, 2017, 32(3):559-562. doi: 10.3904/kjim.2015.372. doi: 10.3904/kjim.2015.372 URL
[22]	Borna S, Nasery A. Spontaneous ovarian hyperstimulation in a pregnant woman with hypothyroidism[J]. Fertil Steril, 2007, 88(3):705.e1-e3. doi: 10.1016/j.fertnstert.2006.12.003. doi: 10.1016/j.fertnstert.2006.12.003
[23]	Scommegna A, Castillo E, Borushek S, et al. Factors in polycystic ovary development. II. Role of the pituitary in the rat[J]. Fertil Steril, 1965, 16:571. doi: org/10.1016/S0015-0282(16)35702-8. doi: org/10.1016/S0015-0282(16)35702-8 pmid: 4284211
[24]	Dobozy O, Csaba G, Hetenyi G, et al. Investigation of gonadotropin-thyrotropin overlapping and hormonal imprinting in the rat testis[J]. Acta Physiol Hung, 1985, 66:169. pmid: 3931416
[25]	Ingbar SH. The thyroid gland[M]// WilsonJD, FosterDW. Textbook of endocrinology. Philadelphia: WB Saun-ders, 1985:682.
[26]	Davis JR, McNeilly JR, Norris AJ, et al. Fetal gonadotrope cell origin of FSH-secreting pituitary Adenoma-insight into human pituitary tumour pathogenesis[J]. Clin Endocrinol(Oxf), 2006, 65(5):648-654. doi: 10.1111/j.1365-265.2006.02644.x. doi: 10.1111/j.1365-265.2006.02644.x. URL
[27]	Eisenberg A, Mersereau J, Buckley AF, et al. Multiple pituitary adenomas with functional follicle-stimulating hormone secretion leading to ovarian hyperstimulation syndrome[J]. AACE Clin Case Rep, 2019, 5(2):e159-e163. doi: 10.4158/ACCR-2018-0474. doi: 10.4158/ACCR-2018-0474
[28]	Knoepfelmacher M, Danilovic DL, Rosa Nasser RH, et al. Effectiveness of treating ovarian hyperstimulation syndrome with cabergoline in two patients with gonadotropin-producing pituitary adenomas[J]. Fertil Steril, 2006, 86(3):719.e15-e18. doi: 10.1016/j.fertnstert.2006.01.055. doi: 10.1016/j.fertnstert.2006.01.055
[29]	Castelo-Branco C, del Pino M, Valladares E. Ovarian hyperstimulation, hyperprolactinaemia and LH gonadotroph adenoma[J]. Reprod Biomed Online, 2009, 19(2):153-155. doi: 10.1016/s1472-6483(10)60065-x. doi: 10.1016/s1472-6483(10)60065-x pmid: 19712547
[30]	Langroudi RM, Amlashi FG, Emami MH. Ovarian cyst regression with levothyroxine in ovarian hyperstimulation syndrome associated with hypothyroidism[J]. Endocrinol Diabetes Metab Case Rep, 2013, 2013:130006. doi: 10.1530/EDM-13-0006. doi: 10.1530/EDM-13-0006
[31]	Murakami T, Higashitsuji H, Yoshinaga K, et al. Management of ovarian hyperstimulation due to follicle-stimulating hormone-secreting gonadotroph adenoma[J]. BJOG, 2004, 111(11):1297-1300. doi: 10.1111/j.1471-0528.2004.00409.x. doi: 10.1111/j.1471-0528.2004.00409.x. URL
[32]	Cooper O, Geller JL, Melmed S. Ovarian hyperstimulation syndrome caused by an FSH-secreting pituitary adenoma[J]. Nat Clin Pract Endocrinol Metab, 2008, 4(4):234-238. doi: 10.1038/ncpendmet0758. doi: 10.1038/ncpendmet0758 URL

参考文献	病理特点	FSH受体基因突变位置	FSH受体突变位置	hCG/TSH 水平	发病机制
Smits等^[5]	家族复发性妊娠早期sOHSS	c.1699G>A p.Asp567Asn	外显子10 （位于第6个跨膜结构域的胞质末端）, 在3个糖蛋白激素受体高度保守	正常	突变受体基础活性增加,对hCG、TSH敏感性增加;细胞实验表明,在表达突变受体的细胞中cAMP异常积累
Vasseur等^[6]	家族复发性妊娠早期sOHSS	c.1346C>T p.Thr449Ile	外显子10 （位于受体第3个跨膜结构域的上部）, 在3个糖蛋白激素受体高度保守	正常	对hCG敏感性增加;外源性hCG使cAMP在表达突变受体的细胞中异常积累
Montanelli等^[7]	家族复发性妊娠早期sOHSS	c.1345A>C p.Thr449Ala	外显子10 （位于第6个跨膜结构域的细胞外末端）,在3个糖蛋白激素受体高度保守	正常	对hCG、TSH异常敏感;细胞实验表明,在表达突变受体的细胞中cAMP异常积累
De Leener等^[8]	妊娠早期sOHSS	c.1636T>C p.Ile554Thr	外显子10 （位于受体第5个跨膜螺旋结构）	正常	对hCG、TSH异常敏感;细胞实验表明,在表达突变受体的细胞中cAMP异常积累
De Leener等^[9]	妊娠早期sOHSS	c.383C>A p.Ser128Tyr	外显子5 （细胞外氨基末端结构域）	正常	对hCG异常敏感;细胞实验表明,外源性hCG使cAMP在表达突变受体的细胞中异常积累
Uchida等^[10]	FSH垂体腺瘤	c.1536G>A p.Met512Ile	外显子10 （位于跨膜结构域）	FSH轻度升高, 生物活性正常	细胞实验表明,显著减少cAMP的产生以及PI3K的磷酸化水平
Chauhan等^[11]	妊娠早期sOHSS	c.1346C>A p.Thr449Asn	外显子10 （位于受体第3个跨膜结构域）	正常	对hCG异常敏感
Hugon-Rodin等^[12]	卵巢蒂扭转	c.1901G>A p.Arg634His	位于受体细胞质的末端	正常	细胞实验表明,在表达突变受体的细胞中cAMP产生减少

参考文献	病理特点	FSH受体基因突变位置	FSH受体突变位置	hCG/TSH 水平	发病机制
Smits等^[5]	家族复发性妊娠早期sOHSS	c.1699G>A p.Asp567Asn	外显子10 （位于第6个跨膜结构域的胞质末端）, 在3个糖蛋白激素受体高度保守	正常	突变受体基础活性增加,对hCG、TSH敏感性增加;细胞实验表明,在表达突变受体的细胞中cAMP异常积累
Vasseur等^[6]	家族复发性妊娠早期sOHSS	c.1346C>T p.Thr449Ile	外显子10 （位于受体第3个跨膜结构域的上部）, 在3个糖蛋白激素受体高度保守	正常	对hCG敏感性增加;外源性hCG使cAMP在表达突变受体的细胞中异常积累
Montanelli等^[7]	家族复发性妊娠早期sOHSS	c.1345A>C p.Thr449Ala	外显子10 （位于第6个跨膜结构域的细胞外末端）,在3个糖蛋白激素受体高度保守	正常	对hCG、TSH异常敏感;细胞实验表明,在表达突变受体的细胞中cAMP异常积累
De Leener等^[8]	妊娠早期sOHSS	c.1636T>C p.Ile554Thr	外显子10 （位于受体第5个跨膜螺旋结构）	正常	对hCG、TSH异常敏感;细胞实验表明,在表达突变受体的细胞中cAMP异常积累
De Leener等^[9]	妊娠早期sOHSS	c.383C>A p.Ser128Tyr	外显子5 （细胞外氨基末端结构域）	正常	对hCG异常敏感;细胞实验表明,外源性hCG使cAMP在表达突变受体的细胞中异常积累
Uchida等^[10]	FSH垂体腺瘤	c.1536G>A p.Met512Ile	外显子10 （位于跨膜结构域）	FSH轻度升高, 生物活性正常	细胞实验表明,显著减少cAMP的产生以及PI3K的磷酸化水平
Chauhan等^[11]	妊娠早期sOHSS	c.1346C>A p.Thr449Asn	外显子10 （位于受体第3个跨膜结构域）	正常	对hCG异常敏感
Hugon-Rodin等^[12]	卵巢蒂扭转	c.1901G>A p.Arg634His	位于受体细胞质的末端	正常	细胞实验表明,在表达突变受体的细胞中cAMP产生减少