卵巢储备功能减退患者再生育的治疗策略

全面二孩政策放开,相当一部分再生育女性进入卵巢储备功能减退（DOR）的年龄。DOR预示卵巢对药物刺激的反应下降,卵母细胞质量不良,发生“受孕难,易流产”的现象,准确、及时评估卵巢储备功能对于拟生育人群至关重要。目前针对DOR人群的生育策略包括：①积极采用辅助生殖技术助孕,其中温和刺激、微刺激或自然周期方案已成为DOR人群的重要方案;②辅以添加生长激素、弱雄激素、抗氧化剂提高助孕成功率;③赠卵体外受精（卵子库的建设）及生殖工程技术。即使先进的助孕技术,对由于年龄原因导致的DOR,仍然很难获得良好的临床妊娠结局。     

卵巢移位联合腹膜阴道延长对卵巢癌患者免疫功能及性生活质量的影响

目的:探讨卵巢移位联合腹膜阴道延长对卵巢癌患者免疫功能及性生活质量的影响。方法:选择2012年4月至2014年12月本院收治的宫颈癌患者80例,按照随机数字法分为两组,各40例,对照组实施常规宫颈癌根治术,观察组在对照组基础上行卵巢移位及腹膜阴道延长。随访12个月。统计两组术后6个月女性性功能质量,干预前后两组免疫球蛋白变化情况,术后6个月时患者阴道长度、开始性生活时间及治疗期间发生并发症情况。结果:观察组性欲望、性兴奋、性高潮、疼痛、阴道潮湿和性满意度6项得分均高于对照组(P0.05),观察组性功能质量评分显著高于对照组(P0.05);干预后两组IgM、Ig G和Ig A水平低于干预前(P0.05),干预后观察组IgM、Ig G和Ig A水平低于干预后对照组(P0.05);观察组术后阴道长度长于对照组(P0.05),开始性生活时间早于对照组(P0.05);观察组发生术后尿潴留、卵巢功能减退、术后阴道狭窄及骨质疏松整体比例低于对照组(P0.05)。结论:卵巢移位联合腹膜阴道延长能有效提高卵巢癌根治术患者术后性生活质量,提高患者机体免疫功能,减少术后因临床功能不全或丧失导致的并发症。     

Primary ovarian mucinous carcinoid tumor: A case report and review of literature

ObjectiveOnly a few cases of primary ovarian mucinous carcinoid tumor have been documented in the literature till date. We present a case of primary ovarian mucinous carcinoid tumor, atypical type, and review the reported cases.Case reportA 33-year-old woman with a left ovarian tumor was diagnosed with primary ovarian mucinous carcinoid tumor, atypical type. She underwent left salpingo-oophorectomy and ipsilateral lymph node dissection. After 5 years, the tumor recurred on the right side, with large para-aortic lymphadenopathy that caused hydronephrosis. Complete surgical staging was performed, followed by nine cycles of weekly paclitaxel and gemcitabine. The tumor progressed after discontinuing the chemotherapy, and the patient died of disease 26 months after recurrence.ConclusionOur patient demonstrated a more aggressive clinical course compared to that reported in previous literature. Based on this experience, complete surgical staging is highly recommended after the patient accomplished her fertility plan. Ovarian carcinoid tumors are relatively chemoresistant compared with epithelial ovarian cancers. The regimen of weekly paclitaxel and gemcitabine stabilized the disease but did not reach remission of the tumor. Further studies are required to determine the appropriate chemotherapy regimen.     

How long is the ovary relevant for synthesis of steroids after menopause?

This study aimed to determine whether the ovaries synthesize estradiol (E2), testosterone (T), and androstenedione (A) after menopause. The first group (30 patients) underwent surgical menopause (SM) – their ovaries were removed due to a benign condition around the time of menopause. The second group (30 patients) consisted of patients with natural menopause (NM). The E2 median level was 10.0?pg/ml (CI?±?2.18) and 9.5?pg/ml (CI?±?1.63) in the NM and SM groups (p?=?.69), respectively. The median level of total T was 0.12?ng/ml (CI?±?0.01) and 0.11?ng/ml (CI?±?0.03) in NM and SM, respectively (p?=?.96). The median level of A was 783.85?pg/ml (CI?±?154.39) and 883.48?pg/dl (CI?±?201.03) in NM and SM, respectively (p?=?.57). The FAI (free androgen index) was 1.06 (CI?±?0.24) and 1.35 (CI?±?0.68) for NM and SM, respectively (p?=?.98). We concluded that 5–10?years after menopause the ovaries are no longer relevant for sex steroid synthesis.     

Prognostic significance of the estrogen receptor beta (ERβ) isoforms ERβ1, ERβ2, and ERβ5 in advanced serous ovarian cancer

Objective

In the present study we have examined the pattern of expression of the full length estrogen receptor β (ERβ1) and two ERβ splice variant isoforms (ERβ2, ERβ5) in well-characterized advanced serous ovarian cancers.

Methods

Immunohistochemistry was performed with ERβ1, ERβ2, and ERβ5 antibodies and results were correlated with pathological and clinical follow-up data. Expression of ERβ isoforms in a panel of ovarian cancer cell lines and human tumor xenografts was also assessed.

Results

Immunohistochemical staining revealed cellular compartment-specific distribution for each isoform in malignant ovarian tissues exhibiting both nuclear staining and cytoplasmic staining. Patients with cytoplasmic ERβ2 expression had significantly worse outcome (p = 0.006 at the multivariate analysis), the 5-year survival rate being nearly 28% for patients who did express cytoplasmic ERβ2, and 60% in negative patients. Cytoplasmic ERβ2 expression was also found to be significantly associated with chemoresistance. In concordance with clinical results both nuclear and cytoplasmic expressions were observed for the three isoforms in the cancer cell lines and human tumor xenografts tested.

Conclusions

This is the first study to uncover an unfavorable prognostic role of ERβ2 in advanced serous ovarian cancer. If anomalies of ERβ2 cytoplasmic expression could be demonstrated to represent an independent unfavorable prognostic marker and/or a marker predicting chemoresistance in advanced serous ovarian cancer, its immunohistochemical assessment at the time of surgery, could help to recognize candidates for clinical trials of new interventions.     

Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum

Objective

To determine whether hormonal therapies have efficacy in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum.

Methods

We searched departmental databases for patients with histologically-confirmed, evaluable, recurrent low-grade serous ovarian or peritoneal carcinoma who received hormonal therapy at our institution between 1989 and 2009. We retrospectively reviewed patients' medical records for demographic, disease, hormonal therapy, and estrogen receptor and progesterone receptor expression data. We used the Response Evaluation Criteria in Solid Tumors version 1.1 to determine patients' responses to hormonal therapy. Because patients could have received more than one evaluable hormonal therapy regimen, we chose to define the outcome metric as “patient-regimens.” Median time to disease progression (TTP) and overall survival (OS) were also calculated. Regression analysis was also performed.

Results

We identified 64 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Patients' median TTP and median OS were 7.4 and 78.2 months, respectively. Patients received 89 separate hormonal patient-regimens, which produced an overall response rate of 9% (6 complete responses and 2 partial responses). Sixty-one percent of the patient-regimens resulted in a progression-free survival duration of at least 6 months. Patient-regimens involving ER +/PR + disease produced a longer median TTP (8.9 months) than patient-regimens involving ER +/PR − disease did (6.2 months; p = 0.053). This difference approached but did not reach statistical significance.

Conclusions

Hormonal therapies have moderate anti-tumor activity in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Further study to determine whether ER/PR expression status is a predictive biomarker for this rare cancer subtype is warranted.     

麻黄素对卵巢组织结构的影响

目的 探讨麻黄素对雌鼠血液雌二醇（E₂）、肾上腺素（EPI）浓度和卵巢组织结构及超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量的影响。 方法 受孕雌鼠分别腹腔注射（2g/L、4g/L、6g/L）麻黄素溶液和等量的生理盐水,采用ELISA法检测15d、20d、25d雌鼠血浆中EPI与E₂浓度的变化,用比色法检测卵巢SOD活性及MDA含量的变化,称量检测卵巢的重量变化,用生物显微技术观察卵巢组织结构的变化,统计卵巢各级卵泡的数量。结果 实验组雌鼠血浆中的E₂含量降低,EPI含量显著升高,并呈现剂量依赖性,卵巢SOD活性降低,MDA含量显著升高;实验组卵巢的重量明显低于对照组,初级卵泡、次级卵泡和闭锁卵泡数量均增多;黄体数量减少;实验组卵巢固缩,结构不完整,卵母细胞萎缩,颗粒细胞变性、降解,排列疏松、紊乱,黄体结构模糊,颗粒黄体细胞核固缩。 结论 麻黄素影响雌鼠卵巢的组织结构和功能,这可能与卵巢中SOD活性下降有关。     

AMH蛋白在性成熟小鼠卵泡发育不同阶段及自然衰老过程卵巢组织中的表达变化

目的:通过检测抗苗勒氏管激素(AMH)蛋白在成年小鼠卵泡发育不同阶段和自然衰老过程卵巢中的表达变化,为卵泡的生长发育调控及卵巢衰老发生发展的机制研究奠定理论基础。方法:选用12,24,36,48周龄自然衰老C57BL/6小鼠为模型。收集12周龄C57BL/6小鼠不同发育阶段的卵巢和24,36,48周龄自然衰老C57BL/6小鼠卵巢。采用免疫组织化学方法和蛋白印迹技术检测各组卵巢中AMH蛋白的表达。结果:免疫组织化学显示,AMH蛋白在始基卵泡、初级卵泡,次级卵泡、窦状卵泡的颗粒细胞中均有表达,但在黄体和闭锁卵泡的颗粒细胞中未见表达。始基卵泡颗粒细胞中AMH蛋白表达明显低于初级卵泡、次级卵泡和窦状卵泡(P<0.05);窦状卵泡颗粒细胞中AMH蛋白表达明显低于初级卵泡和次级卵泡(P<0.05);初级卵泡和次级卵泡的AMH蛋白表达未见明显差异(P>0.05)。不同鼠龄的小鼠同级别卵泡颗粒细胞AMH的染色程度未见明显差异;但是24周龄以后间质中开始出现AMH蛋白表达,并且AMH的表达随鼠龄增加而上升;48周龄小鼠卵巢间质中AMH蛋白表达明显高于24周龄和36周龄(P<0.05);24周龄与36周龄比较差异无统计学意义(P>0.05)。蛋白印迹技术结果显示,AMH蛋白在小鼠卵巢组织中的表达随鼠龄增加而降低,差异有统计学意义(P<0.05)。结论:AMH蛋白主要表达于卵泡发育早期阶段的颗粒细胞,并且其在间质中随鼠龄增加表达增强,但是在整个卵巢组织中其表达量随鼠龄增加而降低。提示AMH可能在卵泡发育以及卵巢衰老中起重要的调控作用。     

Recommendations for fertility preservation in patients with lymphomas

Purpose

This guideline aims to serve as a reference for fertility specialists and other specialists working with young patients at risk of premature ovarian insufficiency (POI) or testicular dysfunction (TD) due to treatment of Hodgkin or Non-Hodgkin lymphoma.

Methods

PubMed search of articles addressing risk of POI and TD according to different treatment protocols used in lymphoma patients. PubMed search of articles presenting different options for fertility treatment in cancer patients.

Results

The risk of POI/TD depends on the protocol used with the highest risk in patients treated with haematopoietic stem cell transplantation/bone marrow transplantation (HSCT/BMT) and the lowest risk in patients treated with ABVD (Adriamycin, Bleomycin, Vincristine and Decarbazine). The different options of fertility preservation are discussed and their relevance according to treatment protocol, age of the patient and urgency to start treatment.

Conclusion

Fertility issues should be discussed with all women of fertile age. Fertility preservation should be offered to young women when relevant. Children should be informed together with their parents. All men should be offered semen cryopreservation regardless of protocol used. At present, there are no established methods of fertility preservation in pre-pubertal boys. This guideline offers suggestions to the most preferred methods of fertility preservation according to treatment protocol, age of the patient, and urgency to start treatment.