体外受精前使用 GnRH 类似物预处理对子宫内膜异位症患者的影响 (ENDOFIV)
一项随机、盲法的比较研究,关于 GnRH 类似物与安慰剂预处理对接受体外受精治疗的子宫内膜异位症不孕症患者的影响
研究概览
详细说明
子宫内膜异位症被定义为引起局部炎症反应的异位子宫内膜组织的存在。 通常,该组织位于骨盆区域的任何水平,但已经描述了骨盆外位置。 这是一种病因不明的慢性疾病,但已证实存在遗传易感性。 据估计,子宫内膜异位症影响了 7-15% 的育龄妇女,高达 30-40% 的子宫内膜异位症妇女不孕。
辅助生殖技术 (ART) 可以治疗多种不孕症,包括子宫内膜异位症。 子宫内膜异位症妇女的辅助生殖结果似乎比没有子宫内膜异位症的妇女的结果差一些。 一些作者已经证明这些患者的着床率和妊娠率显着降低。
最差的妊娠率和植入被认为源于卵母细胞质量差,这可能导致较低的受精率。 这种卵母细胞质量差会产生质量较差的胚胎,植入能力降低,特别是在严重的子宫内膜异位症中。
另一方面,子宫内膜容受性似乎不会降低这些女性的 ART 结果。
为了改善子宫内膜异位症女性的 ART 结果,在周期实现之前提出了不同的策略,并取得了不同的结果。
在 IVF/ICSI 周期之前手术切除子宫内膜异位瘤(子宫内膜异位囊肿)可能会对结果产生不利影响。 另一方面,仔细的腹腔镜膀胱切除术似乎不会影响卵巢对刺激的反应。
除了手术方法外,还尝试了不同的药物治疗来改善子宫内膜异位症女性 IVF/胞浆内单精子注射 (ICSI) 的结果。 有人建议在 IVF 之前使用达那唑治疗可能会改善结果。 同样,在 IVF 前几个月使用 GnRH 类似物延长治疗可以提高着床率和妊娠率。 不幸的是,这些研究中有许多不是随机的和/或对照的,因此在子宫内膜异位症女性的 IVF 之前使用 GnRH 类似物治疗的真正价值仍然需要重视。 最近的一项荟萃分析表明,在 IVF 前使用 GnRH 类似物治疗 3-6 个月可使患有子宫内膜异位症的女性临床妊娠的几率增加 4 倍。 然而,这些结果是从 165 名患者和 78 次怀孕中得出的,包括在 3 项临床试验中,这些试验并非专门针对子宫内膜异位症患者。
缺乏具有适当设计的研究表明,目前没有足够的证据在这方面建立坚定的建议。 这项研究将有助于增加科学证据,以推荐或不推荐在 IVF 子宫内膜异位症患者之前使用 GnRH 激动剂进行预处理。
研究类型
注册 (实际的)
阶段
- 第四阶段
联系人和位置
学习地点
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Valencia、西班牙、46026
- Human Reproduction Unit of the La Fe University and Politechnic Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
纳入标准:
- 在前一年通过手术诊断出患有子宫内膜异位症的不孕女性将其纳入研究,并有残留疾病的迹象和/或阴道生态学中存在卵巢子宫内膜异位瘤,并且对 IVF 治疗敏感。
- 体重指数 < 28 公斤/平方米
- 年龄 < 40 岁
- 签署知情同意书进行试管受精并参与本研究
排除标准:
- 促卵泡激素 (FSH) 第 2-5 个周期日 > 12 IU/L
- 肝脏疾病 (sALAT> 80 IU/L)
- 肾脏疾病(肌酐 > 130 nmol/L)
- 其他禁忌妊娠的相关疾病
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:三倍
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器:GnRHa
在月经周期后的第 1、28 和 56 天皮下注射醋酸曲普瑞林 3.75 mg。
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其他名称:
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安慰剂比较:生理血清
在月经周期后第 1、28 和 56 天施用生理血清皮下注射,使用与活性比较剂相同的递送装置和相同体积。
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其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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按开始周期划分的临床妊娠率
大体时间:妊娠生化诊断后2周
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超声检查有胎心跳动的妊娠数除以开始周期总数
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妊娠生化诊断后2周
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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回收的卵母细胞数量、总数和中期 II
大体时间:在取卵的那一刻
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在取卵的那一刻
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胚胎质量
大体时间:卵母细胞恢复和 IVF 后两三天
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卵母细胞恢复和 IVF 后两三天
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子宫内膜异位囊肿的数量和大小
大体时间:基础超声日
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每个卵巢的总数,单侧或双侧囊肿和最大子宫内膜异位囊肿的最大直径(mm)
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基础超声日
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子宫内膜异位症/子宫内膜异位症患者的妊娠至足月率
大体时间:周期后 37 周
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妊娠第 37 至 41 周的分娩数除以妊娠总数
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周期后 37 周
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流产率
大体时间:怀孕第22周
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流产次数除以临床妊娠总数
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怀孕第22周
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健康活产率
大体时间:怀孕第 37 至 41 周
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健康活产数除以开始周期总数
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怀孕第 37 至 41 周
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受精率
大体时间:卵母细胞恢复和 IVF 后两天
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卵裂胚胎数除以中期 II 卵母细胞总数
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卵母细胞恢复和 IVF 后两天
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促性腺激素的总剂量和治疗天数
大体时间:人绒毛膜促性腺激素 (hCG) 给药日
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IU 中的促性腺激素总剂量和治疗总天数
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人绒毛膜促性腺激素 (hCG) 给药日
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取消率及原因
大体时间:促性腺激素治疗的最后一天
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取消的周期数除以总数或开始的周期数
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促性腺激素治疗的最后一天
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卵巢过度刺激综合症 (OHSS) 的发病率
大体时间:HCG 后一个月
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诊断为 OHSS 的患者人数除以结束周期。
分为轻度、中度和重度
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HCG 后一个月
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合作者和调查者
调查人员
- 首席研究员:ANA Mª MONZÓ, MD, PhD、La Fe University Hospital
出版物和有用的链接
一般刊物
- Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006 Jan 25;2006(1):CD004635. doi: 10.1002/14651858.CD004635.pub2.
- Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002 Jun;77(6):1148-55. doi: 10.1016/s0015-0282(02)03112-6.
- Matson PL, Yovich JL. The treatment of infertility associated with endometriosis by in vitro fertilization. Fertil Steril. 1986 Sep;46(3):432-4. doi: 10.1016/s0015-0282(16)49581-6.
- Simon C, Gutierrez A, Vidal A, de los Santos MJ, Tarin JJ, Remohi J, Pellicer A. Outcome of patients with endometriosis in assisted reproduction: results from in-vitro fertilization and oocyte donation. Hum Reprod. 1994 Apr;9(4):725-9. doi: 10.1093/oxfordjournals.humrep.a138578.
- Cahill DJ, Wardle PG, Maile LA, Harlow CR, Hull MG. Ovarian dysfunction in endometriosis-associated and unexplained infertility. J Assist Reprod Genet. 1997 Nov;14(10):554-7. doi: 10.1023/a:1022568331845.
- Norenstedt SN, Linderoth-Nagy C, Bergendal A, Sjoblom P, Bergqvist A. Reduced developmental potential in oocytes from women with endometriosis. J Assist Reprod Genet. 2001 Dec;18(12):644-9. doi: 10.1023/a:1013111200251.
- Nakahara K, Saito H, Saito T, Ito M, Ohta N, Takahashi T, Hiroi M. Ovarian fecundity in patients with endometriosis can be estimated by the incidence of apoptotic bodies. Fertil Steril. 1998 May;69(5):931-5. doi: 10.1016/s0015-0282(98)00038-7.
- Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril. 1998 Sep;70(3):425-31. doi: 10.1016/s0015-0282(98)00204-0.
- Toya M, Saito H, Ohta N, Saito T, Kaneko T, Hiroi M. Moderate and severe endometriosis is associated with alterations in the cell cycle of granulosa cells in patients undergoing in vitro fertilization and embryo transfer. Fertil Steril. 2000 Feb;73(2):344-50. doi: 10.1016/s0015-0282(99)00507-5.
- Aboulghar MA, Mansour RT, Serour GI, Al-Inany HG, Aboulghar MM. The outcome of in vitro fertilization in advanced endometriosis with previous surgery: a case-controlled study. Am J Obstet Gynecol. 2003 Feb;188(2):371-5. doi: 10.1067/mob.2003.13.
- Tei C, Miyazaki T, Kuji N, Tanaka M, Sueoka K, Yoshimura Y. Effect of danazol on the pregnancy rate in patients with unsuccessful in vitro fertilization-embryo transfer. J Reprod Med. 1998 Jun;43(6):541-6.
- Marcus SF, Edwards RG. High rates of pregnancy after long-term down-regulation of women with severe endometriosis. Am J Obstet Gynecol. 1994 Sep;171(3):812-7. doi: 10.1016/0002-9378(94)90103-1.
- Chedid S, Camus M, Smitz J, Van Steirteghem AC, Devroey P. Comparison among different ovarian stimulation regimens for assisted procreation procedures in patients with endometriosis. Hum Reprod. 1995 Sep;10(9):2406-11. doi: 10.1093/oxfordjournals.humrep.a136308.
- Ruiz-Velasco V, Allende S. Goserelin followed by assisted reproduction: results in infertile women with endometriosis. Int J Fertil Womens Med. 1998 Jan-Feb;43(1):18-23.
- Suganuma N, Wakahara Y, Ishida D, Asano M, Kitagawa T, Katsumata Y, Moriwaki T, Furuhashi M. Pretreatment for ovarian endometrial cyst before in vitro fertilization. Gynecol Obstet Invest. 2002;54 Suppl 1:36-40; discussion 41-2. doi: 10.1159/000066293.
- Arici A, Oral E, Bukulmez O, Duleba A, Olive DL, Jones EE. The effect of endometriosis on implantation: results from the Yale University in vitro fertilization and embryo transfer program. Fertil Steril. 1996 Mar;65(3):603-7. doi: 10.1016/s0015-0282(16)58162-x.
- Inoue M, Kobayashi Y, Honda I, Awaji H, Fujii A. The impact of endometriosis on the reproductive outcome of infertile patients. Am J Obstet Gynecol. 1992 Jul;167(1):278-82. doi: 10.1016/s0002-9378(11)91675-5.
- Dmowski WP, Rana N, Michalowska J, Friberg J, Papierniak C, el-Roeiy A. The effect of endometriosis, its stage and activity, and of autoantibodies on in vitro fertilization and embryo transfer success rates. Fertil Steril. 1995 Mar;63(3):555-62. doi: 10.1016/s0015-0282(16)57425-1.
- Olivennes F, Feldberg D, Liu HC, Cohen J, Moy F, Rosenwaks Z. Endometriosis: a stage by stage analysis--the role of in vitro fertilization. Fertil Steril. 1995 Aug;64(2):392-8. doi: 10.1016/s0015-0282(16)57740-1.
- Tanbo T, Omland A, Dale PO, Abyholm T. In vitro fertilization/embryo transfer in unexplained infertility and minimal peritoneal endometriosis. Acta Obstet Gynecol Scand. 1995 Aug;74(7):539-43. doi: 10.3109/00016349509024386.
- Huang HY, Lee CL, Lai YM, Chang MY, Chang SY, Soong YK. The outcome of in vitro fertilization and embryo transfer therapy in women with endometriosis failing to conceive after laparoscopic conservative surgery. J Am Assoc Gynecol Laparosc. 1997 May;4(3):299-303. doi: 10.1016/s1074-3804(05)80219-1.
- Hickman TN. Impact of endometriosis on implantation. Data from the Wilford Hall Medical Center IVF-ET Program. J Reprod Med. 2002 Oct;47(10):801-8.
- Wardle PG, Mitchell JD, McLaughlin EA, Ray BD, McDermott A, Hull MG. Endometriosis and ovulatory disorder: reduced fertilisation in vitro compared with tubal and unexplained infertility. Lancet. 1985 Aug 3;2(8449):236-9. doi: 10.1016/s0140-6736(85)90289-2.
- Hull MG, Williams JA, Ray B, McLaughlin EA, Akande VA, Ford WC. The contribution of subtle oocyte or sperm dysfunction affecting fertilization in endometriosis-associated or unexplained infertility: a controlled comparison with tubal infertility and use of donor spermatozoa. Hum Reprod. 1998 Jul;13(7):1825-30. doi: 10.1093/humrep/13.7.1825.
- Bergendal A, Naffah S, Nagy C, Bergqvist A, Sjoblom P, Hillensjo T. Outcome of IVF in patients with endometriosis in comparison with tubal-factor infertility. J Assist Reprod Genet. 1998 Oct;15(9):530-4. doi: 10.1023/a:1022526002421.
- Pal L, Shifren JL, Isaacson KB, Chang Y, Leykin L, Toth TL. Impact of varying stages of endometriosis on the outcome of in vitro fertilization-embryo transfer. J Assist Reprod Genet. 1998 Jan;15(1):27-31. doi: 10.1023/a:1022574221115.
- O'Shea RT, Chen C, Weiss T, Jones WR. Endometriosis and in-vitro fertilisation. Lancet. 1985 Sep 28;2(8457):723. doi: 10.1016/s0140-6736(85)92957-5. No abstract available.
- Yovich JL, Yovich JM, Tuvik AI, Matson PL, Willcox DL. In-vitro fertilisation for endometriosis. Lancet. 1985 Sep 7;2(8454):552. doi: 10.1016/s0140-6736(85)90485-4. No abstract available.
- Garrido N, Navarro J, Remohi J, Simon C, Pellicer A. Follicular hormonal environment and embryo quality in women with endometriosis. Hum Reprod Update. 2000 Jan-Feb;6(1):67-74. doi: 10.1093/humupd/6.1.67.
- Pellicer A, Valbuena D, Bauset C, Albert C, Bonilla-Musoles F, Remohi J, Simon C. The follicular endocrine environment in stimulated cycles of women with endometriosis: steroid levels and embryo quality. Fertil Steril. 1998 Jun;69(6):1135-41. doi: 10.1016/s0015-0282(98)00085-5.
- Smith MP, Keay SD, Margo FC, Harlow CR, Wood PJ, Cahill DJ, Hull MG. Total cortisol levels are reduced in the periovulatory follicle of infertile women with minimal-mild endometriosis. Am J Reprod Immunol. 2002 Jan;47(1):52-6. doi: 10.1034/j.1600-0897.2002.1o122.x.
- Cunha-Filho JS, Lemos NA, Freitas FM, Kiefer K, Faller M, Passos EP. Insulin-like growth factor (IGF)-1 and IGF binding protein-1 and -3 in the follicular fluid of infertile patients with endometriosis. Hum Reprod. 2003 Feb;18(2):423-8. doi: 10.1093/humrep/deg077.
- Carlberg M, Nejaty J, Froysa B, Guan Y, Soder O, Bergqvist A. Elevated expression of tumour necrosis factor alpha in cultured granulosa cells from women with endometriosis. Hum Reprod. 2000 Jun;15(6):1250-5. doi: 10.1093/humrep/15.6.1250.
- Sung L, Mukherjee T, Takeshige T, Bustillo M, Copperman AB. Endometriosis is not detrimental to embryo implantation in oocyte recipients. J Assist Reprod Genet. 1997 Mar;14(3):152-6. doi: 10.1007/BF02766132.
- Pellicer A, Oliveira N, Ruiz A, Remohi J, Simon C. Exploring the mechanism(s) of endometriosis-related infertility: an analysis of embryo development and implantation in assisted reproduction. Hum Reprod. 1995 Dec;10 Suppl 2:91-7. doi: 10.1093/humrep/10.suppl_2.91.
- Ho HY, Lee RK, Hwu YM, Lin MH, Su JT, Tsai YC. Poor response of ovaries with endometrioma previously treated with cystectomy to controlled ovarian hyperstimulation. J Assist Reprod Genet. 2002 Nov;19(11):507-11. doi: 10.1023/a:1020970417778.
- Canis M, Pouly JL, Tamburro S, Mage G, Wattiez A, Bruhat MA. Ovarian response during IVF-embryo transfer cycles after laparoscopic ovarian cystectomy for endometriotic cysts of >3 cm in diameter. Hum Reprod. 2001 Dec;16(12):2583-6. doi: 10.1093/humrep/16.12.2583.
- Marconi G, Vilela M, Quintana R, Sueldo C. Laparoscopic ovarian cystectomy of endometriomas does not affect the ovarian response to gonadotropin stimulation. Fertil Steril. 2002 Oct;78(4):876-8. doi: 10.1016/s0015-0282(02)03326-5.
- Donnez J, Wyns C, Nisolle M. Does ovarian surgery for endometriomas impair the ovarian response to gonadotropin? Fertil Steril. 2001 Oct;76(4):662-5. doi: 10.1016/s0015-0282(01)02011-8.
- Wyns C, Donnez J. [Laser vaporization of ovarian endometriomas: the impact on the response to gonadotrophin stimulation]. Gynecol Obstet Fertil. 2003 Apr;31(4):337-42. doi: 10.1016/s1297-9589(03)00069-9. French.
- Garcia-Velasco JA, Mahutte NG, Corona J, Zuniga V, Giles J, Arici A, Pellicer A. Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study. Fertil Steril. 2004 May;81(5):1194-7. doi: 10.1016/j.fertnstert.2003.04.006.
- Dicker D, Goldman JA, Feldberg D, Ashkenazi J, Levy T. Transvaginal ultrasonic needle-guided aspiration of endometriotic cysts before ovulation induction for in vitro fertilization. J In Vitro Fert Embryo Transf. 1991 Oct;8(5):286-9. doi: 10.1007/BF01139786.
- Dicker D, Ashkenazi J, Feldberg D, Levy T, Dekel A, Ben-Rafael Z. Severe abdominal complications after transvaginal ultrasonographically guided retrieval of oocytes for in vitro fertilization and embryo transfer. Fertil Steril. 1993 Jun;59(6):1313-5. doi: 10.1016/s0015-0282(16)55997-4.
- Yaron Y, Peyser MR, Samuel D, Amit A, Lessing JB. Infected endometriotic cysts secondary to oocyte aspiration for in-vitro fertilization. Hum Reprod. 1994 Sep;9(9):1759-60. doi: 10.1093/oxfordjournals.humrep.a138789.
- Nargund G, Parsons J. Infected endometriotic cysts secondary to oocyte aspiration for in-vitro fertilization. Hum Reprod. 1995 Jun;10(6):1555. doi: 10.1093/humrep/10.6.1555-a. No abstract available.
- Younis JS, Ezra Y, Laufer N, Ohel G. Late manifestation of pelvic abscess following oocyte retrieval, for in vitro fertilization, in patients with severe endometriosis and ovarian endometriomata. J Assist Reprod Genet. 1997 Jul;14(6):343-6. doi: 10.1007/BF02765839.
- Wei CF, Chen SC. Pelvic abscess after ultrasound-guided aspiration of endometrioma: a case report. Zhonghua Yi Xue Za Zhi (Taipei). 1998 Oct;61(10):603-7.
- Kim CH, Chae HD, Kang BM, Chang YS, Mok JE. The immunotherapy during in vitro fertilization and embryo transfer cycles in infertile patients with endometriosis. J Obstet Gynaecol Res. 1997 Oct;23(5):463-70. doi: 10.1111/j.1447-0756.1997.tb00874.x.
- Oehninger S, Brzyski RG, Muasher SJ, Acosta AA, Jones GS. In-vitro fertilization and embryo transfer in patients with endometriosis: impact of a gonadotrophin releasing hormone agonist. Hum Reprod. 1989 Jul;4(5):541-4. doi: 10.1093/oxfordjournals.humrep.a136941.
- Dicker D, Goldman GA, Ashkenazi J, Feldberg D, Voliovitz I, Goldman JA. The value of pre-treatment with gonadotrophin releasing hormone (GnRH) analogue in IVF-ET therapy of severe endometriosis. Hum Reprod. 1990 May;5(4):418-20. doi: 10.1093/oxfordjournals.humrep.a137114.
- Dale PO, Tanbo T, Abyholm T. Endometriosis-associated infertility treated by long-term gonadotropin-releasing hormone agonist administration and assisted fertilization. J In Vitro Fert Embryo Transf. 1990 Jun;7(3):180-1. doi: 10.1007/BF01135686.
- Nakamura K, Oosawa M, Kondou I, Inagaki S, Shibata H, Narita O, Suganuma N, Tomoda Y. Menotropin stimulation after prolonged gonadotropin releasing hormone agonist pretreatment for in vitro fertilization in patients with endometriosis. J Assist Reprod Genet. 1992 Apr;9(2):113-7. doi: 10.1007/BF01203749.
- Curtis P, Jackson A, Bernard A, Shaw RW. Pretreatment with gonadotrophin releasing hormone (GnRH) analogue prior to in vitro fertilisation for patients with endometriosis. Eur J Obstet Gynecol Reprod Biol. 1993 Dec 30;52(3):211-6. doi: 10.1016/0028-2243(93)90074-m.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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