The Possible Association between IVF and Breast Cancer Incidence

Background The possible association between ovulation-inducing drugs and breast cancer development has been debated. Our aim was to evaluate the incidence of breast cancer in a cohort of women exposed to in vitro fertilization (IVF). Methods A retrospective cohort analysis was performed by linkage of the computerized database of all women treated at the IVF Unit at Assaf Harofeh Medical Center between 1986 and 2003, and the Israeli National Cancer Registry. The standardized incidence ratio (SIR) was computed as the ratio between the observed number of breast cancer cases and the expected cases, adjusted for age and continent of birth, in the general population. Tumor characteristics of the IVF patients were studied by reviewing original medical records. Results 35 breast carcinomas were diagnosed among 3,375 IVF-treated women, compared to 24.8 cases expected (SIR = 1.4; 95% CI 0.98–1.96). Age ≥40 years at IVF treatment (SIR = 1.9; 95% CI 0.97–3.30), hormonal infertility (SIR = 3.1; 95% CI 0.99–7.22), and ≥4 IVF cycles (SIR = 2.0; 95% CI 1.15–3.27) were found to be risk factors to develop breast cancer compared to the general population. Multivariate analysis revealed that women who underwent ≥4 IVF cycles compared to those with one to three cycles were at risk to develop breast cancer, although not significantly (SIR = 1.9; 95% CI 0.95–3.81). Of IVF-treated women 85% had ER(+) tumors and 29% had positive family history. Conclusions A possible association between IVF therapy and breast cancer development was demonstrated, especially in women ≥40 years of age. These preliminary findings need to be replicated in other cohort studies.     

垂体降调节与卵泡发育同步化的研究进展

人类生殖周期以单卵泡发育排卵为特征,辅助生殖技术应用垂体降调节控制性促排卵可以促使多个卵泡发育,获取更多卵母细胞,但因年龄增长、卵巢反应不均和多囊卵巢综合征等原因却无法避免卵泡生长发育的不同步现象.根据患者临床适应证选择合理的降调节促排卵方案,可以通过调整促性腺激素释放激素激动剂(GnRHa)剂量和使用时间、辅助用药以及大卵泡穿刺等方式改善促排卵过程中卵泡发育不同步的现象,以期获得较好的临床结局.     

石英毓麟汤治疗不孕症临床研究

石英毓麟汤是治疗肾虚不孕症的自拟方,具有促排卵和健全黄体功能的作用,除治疗不孕症外,尚可用于治疗各种因排卵障碍所致的月经后期、月经先后不定期、闭经和功能性子宫出血等。用于治疗不孕症215例,受孕141例,受孕率为65.6％。动物实验证明,本方可使幼鼠卵巢重量增加,使成年小白鼠的排卵数目及妊子数比对照组明显增加。     

人类体外受精与胚胎移植

收治不孕妇女34例,42个治疗周期,采用固定的Fertilin/Pergonal/Profasi超排方案,B超监测卵泡发育并指导经阴道取卵。每周期有6.97±4.1个卵泡发育。获得卵子4.7±4.6个,受精率为71％,卵裂率64％,移植率87.8％。每周期移植的胚胎总分与移植后妊娠率有显著相关性(r=0.8823,P=0.0086),移植胚胎评分高,数量多,妊娠率越高。本组5例妊娠中有3例移植6个胚胎以上。在未建立胚胎冻存技术之前,4个以上的胚胎移植是处理过剩胚胎的权衡方法。本组大部分病人在门诊接受治疗,减轻精神与经济负担。     

Effects of acute stress on the day of proestrus on sexual behavior and ovulation in female rats: participation of the angiotensinergic system

Physical or emotional stress can affect the female reproductive physiology and angiotensin II (Ang II) is a hormone that participates in the stress response and also in the control of reproductive hormones. The present study aimed at evaluating the effects of acute stress in the morning and afternoon of proestrus on sexual behavior and ovulation and the participation of Ang II in the stress-induced effects. Female rats with regular estrous cycles were used. Several different stress protocols were tested in the morning and in the afternoon of proestrus: restraint stress 10 min; restraint stress 1 h and ether stress, respectively. The participation of Ang II was evaluated by injecting Ang II receptor antagonists (losartan and PD123319) 15 min before stress. The lordosis quotient was recorded and the number of oocytes was counted. Plasma levels of luteinizing hormone, progesterone, prolactin and corticosterone were measured. All types of stress in the morning of proestrus induced a reduction in the number of oocytes. Restraint stress (1 h) in the afternoon of proestrus induced a significant reduction in the lordosis quotient. Peripheral and central losartan, but not PD123319, injections partly reverted the effects of stress on ovulation in the morning of proestrus. Acute stress in the morning of proestrus also reduced luteinizing hormone, progesterone and prolactin surges later on the same day. In conclusion, acute stress on the day of proestrus can affect female reproductive physiology. Moreover, the angiotensinergic system, through AT(1) receptors, participates in the effects of acute stress in the morning of proestrus.     

Effectiveness of levonorgestrel emergency contraception given before or after ovulation--a pilot study

BACKGROUND: Although widely used, the mechanisms of action of the levonorgestrel emergency contraceptive pill (LNG ECP) are still unclear. There are increasing data to indicate that LNG is particularly effective as an ECP by interrupting follicular development and ovulation. An important outstanding question is whether it has any effect on fertilization or implantation. METHOD: Ninety-nine women participated; they were recruited at the time they presented with a request for emergency contraception. All women took LNG 1.5 mg in a single dose during the clinic consultation. A blood sample was taken immediately prior to ingestion of the ECP for estimation of serum LH, estradiol and progesterone levels to calculate the day of ovulation. The specimens were analyzed in a single batch. Based on these endocrine data, we estimated the timing of ovulation to be within a +/-24-h period with an accuracy of around 80%. Women were followed up 4-6 weeks later to ascertain pregnancy status. The effectiveness of ECP when taken before and after ovulation was determined. RESULTS: Three women became pregnant despite taking the ECP (pregnancy rate, 3.0%). All three women who became pregnant had unprotected intercourse between Days -1 and 0 and took the ECP on Day +2, based on endocrine data. Day 0 was taken as ovulation day. Among 17 women who had intercourse in the fertile period of the cycle and took the ECP after ovulation occurred (on Days +1 to +2), we could have expected three or four pregnancies; three were observed. Among 34 women who had intercourse on Days -5 to -2 of the fertile period and took ECP before or on the day of ovulation, four pregnancies could have been expected, but none were observed. We found major discrepancies between women's self-report of stage of the cycle and the dating calculation based on endocrine data. CONCLUSION: These data are supportive of the concept that the LNG ECP has little or no effect on postovulation events but is highly effective when taken before ovulation.     

Effects of guanethidine administration on compensatory ovarian hypertrophy,compensatory ovulation and follicular development in the prepubertal female guinea pig

We analyzed the participation of sympathetic ovarian innervation in the prepubertal female guinea pig on regulation of compensatory ovarian hypertrophy (COH) and compensatory ovulation at puberty. The COH of the left ovary was significantly higher that of the right one (left ovary: 41.5+/-5.2 vs. 27.5+/-5.6%, p<0.05, Kruskal-Wallis test). The sympathetic denervation induced by guanethidine administration beginnings at birth or on day 10 resulted in a significant increase of the COH by each ovary (p<0.05, Kruskal-Wallis test). Only one of the six untreated control guinea pigs sacrificed at the follicular phase ovulate. All the hemiovariectomized animals with the left ovary in situ ovulated, while only two out of five with the right ovary in situ did (100 vs. 40%: p<0.001, Kruskal-Wallis test), unlike the denervated animals, which did not ovulate. The number of corpora lutea present in the ovaries was similar among all groups of animals. These results demonstrate differences in the follicular diameter in untreated female guinea pigs and add further support to the concept of asymmetrical response of the ovaries to denervation.     

女性低促性腺激素性性腺功能减退症诱导排卵治疗进展

女性低促性腺激素性性腺功能减退症(HH)是下丘脑或垂体病变导致卵巢功能低下的一类疾病.雌孕激素替代治疗可促进和维持女性第二性征发育及人工月经周期对于有生育要求的患者,补充促性腺激素释放激素或促性腺激素可诱导患者卵泡发育、排卵,甚至妊娠.本文主要讨论女性HH患者的诱导排卵治疗进展.     

来曲唑联合尿促性素用于排卵障碍患者促排卵效果观察

目的:比较来曲唑(LE)联合尿促性素(HMG)与他莫昔芬(TMX)联合HMG对排卵障碍患者的促排卵效果及其对生殖激素的影响。方法:拟行促排卵治疗的197例排卵障碍不孕症患者随机分实验LE+HMG组(105例、211周期)和对照TMX+HMG组(92例、201周期),实验组于月经周期第3～7天口服LE 5.0 mg/d共5天,第8天起肌注HMG 75～150U/d至HCG日;对照组于月经周期第5～9天口服TMX 10 mg,2次/d共5天,第10天起肌注HMG 75～150 U/d至HCG日。超声监测卵泡发育,并于月经周期第8天和HCG注射日取静脉血测定黄体生成素(LH)、雌二醇(E2)、睾酮(T);观察优势卵泡数、成熟卵泡数、排卵率、妊娠率、子宫内膜厚度、多胎妊娠率、卵巢过度刺激综合征(OHSS)发生率及生殖激素变化。结果:LE+HMG组的排卵率和周期妊娠率与TMX+HMG组相似(P>0.05),HCG日其优势卵泡数和成熟卵泡数均显著低于TMX+HMG组(P<0.05)。两组在HCG日子宫内膜的厚度无明显差异(P>0.05),其在月经周期第8天和HCG日的血清E2水平均显著低于TMX+HMG组(P<0.05),血清T水平及LH水平两组无明显差异(P>0.05)。LE+HMG组未发生1例OHSS及多胎妊娠。结论:LE+HMG用于排卵障碍的不孕症妇女具有良好的排卵率和周期妊娠率,且并发症低。     

芬吗通联合坤泰胶囊对卵巢储备功能低下性不孕的预处理及促排治疗

目的：探讨芬吗通联合坤泰胶囊治疗卵巢功能低下（decreasing ovarian reserve,DOR）的临床效果及促排卵后的受孕情况。方法选取2012年1月～2013年7月收治的57例DOR患者,芬吗通联合坤泰胶囊治疗3个月,检测卵泡刺激素（FSH）、促黄体生成素（LH）、雌二醇（E 2）、抗苗勒管激素（AMH）、窦卵泡数、卵巢体积、动脉收缩期峰值流速（PSV）。治疗前后采用自身对照。结果 FSH、LH水平较治疗前下降,E 2、AMH、窦卵泡数、PSV水平较治疗前上升,差异有统计学意义（P＜0.05）,卵巢体积较治疗前增加,但差异无统计学意义。联合治疗后给予来曲唑促排卵受孕率提高。结论芬吗通联合坤泰胶囊治疗卵巢功能低下,可有效改善卵巢储备,加以促排卵治疗,提高DOR患者的受孕成功率。