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化疗期间促性腺激素释放激素激动剂联合治疗可能提高幸存者的妊娠率。

Gonadotropin-Releasing Hormone Agonist Cotreatment During Chemotherapy May Increase Pregnancy Rate in Survivors.

作者信息

Blumenfeld Zeev, Zur Hilli, Dann Eldad J

机构信息

Department of Gynecology and Obstetrics, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Department of Reproductive Endocrinology, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

Department of Reproductive Endocrinology, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

出版信息

Oncologist. 2015 Nov;20(11):1283-9. doi: 10.1634/theoncologist.2015-0223. Epub 2015 Oct 13.

Abstract

BACKGROUND

The use of gonadotropin-releasing hormone analogs (GnRHas) for fertility preservation is not unequivocally accepted. It is controversial whether GnRHa can increase the pregnancy rate in survivors.

PATIENTS AND METHODS

This is a retrospective cohort study. Every patient referred for fertility preservation was offered cryopreservation of embryos, ova, and ovarian tissue and GnRHa. The patients were consecutively included. The primary outcome was spontaneous pregnancies. The secondary outcome was cyclic ovarian function (COF) versus premature ovarian failure (POF). These outcomes were assessed 2 years or more after chemotherapy.

RESULTS

We compared 286 patients who received gonadotropin-releasing hormone agonist (GnRHa) with chemotherapy with 188 patients who were treated with chemotherapy alone. Ovarian function could be determined in 217 patients. Overall, 87% (127 of 146) of the patients in the GnRHa group retained COF and 13% (19 of 146) suffered POF, whereas in the control group, 49% (35 of 71) experienced COF and 51% (36 of 71) suffered POF (p = .0001). The odds ratio (OR) for preserving COF was 6.87 for the patients who received GnRHa (95% confidence interval [CI] 3.4-13.4). Overall 60% (112 of 188) of the survivors conceived: 69.3% (84 of 122) of the patients in the GnRHa group compared with 42.4% (28 of 66) in the control group (p = .006). In the GnRHa group, 123 healthy newborns were delivered, versus 40 in the controls. Spontaneous pregnancies occurred in 65.6% (80 of 122) of the survivors in the GnRHa group versus 37.9% (25 of 66) in the control group (p = .0004, OR 3.12, 95% CI 1.7-5.8).

CONCLUSION

Adding GnRHa to chemotherapy significantly increases the OR for spontaneous conception, in addition to COF. It is suggested that GnRHa cotreatment should be added before and during gonadotoxic chemotherapy.

IMPLICATIONS FOR PRACTICE

The use of gonadotropin-releasing hormone analogs (GnRHa) for fertility preservation is not unequivocally accepted and is even controversial. This study compared 286 patients who received GnRHa with chemotherapy with 188 patients who were treated with chemotherapy alone. Ovarian function could be determined in 217 patients. The odds ratio for preserving cyclic ovarian function was 6.87 for the patients who received GnRHa. Furthermore, the total and spontaneous pregnancy rate was significantly higher for those who received the agonist (p = .006). Adding GnRHa to chemotherapy significantly increased the odds ratio for spontaneous conception, in addition to preserving regular ovarian function. It is suggested that GnRHa cotreatment should be administered to young women in conjunction with gonadotoxic chemotherapy.

摘要

背景

促性腺激素释放激素类似物(GnRHas)用于生育力保存尚未得到明确认可。GnRHa能否提高幸存者的妊娠率存在争议。

患者与方法

这是一项回顾性队列研究。每一位前来寻求生育力保存的患者都接受了胚胎、卵子和卵巢组织的冷冻保存以及GnRHa治疗。患者连续纳入。主要结局是自然妊娠。次要结局是周期性卵巢功能(COF)与卵巢早衰(POF)。这些结局在化疗后2年或更长时间进行评估。

结果

我们将286例接受促性腺激素释放激素激动剂(GnRHa)联合化疗的患者与188例单纯接受化疗的患者进行了比较。217例患者的卵巢功能可被评估。总体而言,GnRHa组87%(146例中的127例)的患者保留了COF,13%(146例中的19例)发生了POF,而在对照组中,49%(71例中的35例)经历了COF,51%(71例中的36例)发生了POF(p = 0.0001)。接受GnRHa治疗的患者保留COF的优势比(OR)为6.87(95%置信区间[CI] 3.4 - 13.4)。总体而言,60%(188例中的112例)的幸存者受孕:GnRHa组69.3%(122例中的84例)的患者,而对照组为42.4%(66例中的28例)(p = 0.006)。在GnRHa组,有123例健康新生儿出生,而对照组为40例。GnRHa组65.6%(122例中的80例)的幸存者发生了自然妊娠,而对照组为37.9%(66例中的25例)(p = 0.0004,OR 3.12,95% CI 1.7 - 5.8)。

结论

在化疗中添加GnRHa除了能提高COF外,还显著增加了自然受孕的OR。建议在性腺毒性化疗之前和期间添加GnRHa联合治疗。

对实践的启示

促性腺激素释放激素类似物(GnRHas)用于生育力保存尚未得到明确认可,甚至存在争议。本研究将286例接受GnRHa联合化疗的患者与188例单纯接受化疗的患者进行了比较。217例患者的卵巢功能可被评估。接受GnRHa治疗的患者保留周期性卵巢功能的优势比为6.87。此外,接受激动剂治疗的患者的总妊娠率和自然妊娠率显著更高(p = 0.006)。在化疗中添加GnRHa除了能保持正常卵巢功能外,还显著增加了自然受孕的优势比。建议对年轻女性在性腺毒性化疗时给予GnRHa联合治疗。

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