Pro-caspase-3 is constitutively expressed in luteinized granulosa cells from women undergoing controlled ovarian stimulation for in vitro fertilization

Apoptosis regulation in luteinized granulosa cells (LGC) during assisted reproduction procedures is still controversial. Caspase-3 is a major apoptosis mediator encoded by CASP3 and formed through cleavage of its precursor pro-caspase-3. The aim of this study was to investigate the expression patterns of pro-caspase-3 (mRNA and protein) and cleaved caspase-3 in human LGC. Thirty-five women undergoing controlled ovarian stimulation for in vitro fertilization were prospectively enrolled in the study. LGC were isolated from follicular fluid during oocyte pickup and evaluated by immunocytochemistry for pro-caspase-3 and cleaved caspase-3, and by real-time PCR for CASP3 mRNA expression. We found a positive staining of pro-caspase-3 in 77 % of the LGC (95 % confidence interval [CI] 60%–84%), whereas cleaved caspase-3 was found in only 4% of the cells (95 % CI 3%–6%). The abundance of cells expressing pro-caspase-3 was independent from CASP3 mRNA levels (r = 0.24, p = 0.255) and did not correlate with the amount of cleaved caspase-3 (r = -0.24, p = 0.186). Multivariable logistic regression showed that pro-caspase-3 positivity was not influenced by clinical characteristics such as age, cause or length of infertility, antral follicle count or hormonal drugs used to induce ovulation. These findings suggest that pro-caspase-3 is constitutively expressed in LGC, allowing quick cleavage into active caspase-3 and apoptosis triggering whenever needed in the course of gonadotropin-induced follicular development.     

Adjuvants in IVF—evidence for what works and what does not work

The field of assisted reproductive technology is shaped and changed constantly by advances in science and cutting-edge innovations. In a quest to maximise outcomes, add-on interventions are often adopted and utilised prematurely while the principles of evidence-based medicine seem to be less strictly adhered to. In this review we will attempt to summarise the latest evidence about some of the adjuvants.     

卵巢肿瘤保守性手术后IVF助孕的安全性和有效性

随着卵巢肿瘤筛查的普及和诊治水平的提高,早期诊断和治疗提高了该类患者的生存期以及生活质量,同时也让更多年轻的卵巢肿瘤患者保留了生育的机会。然而,由于手术及放、化疗等原因,部分卵巢肿瘤患者术后常常出现不孕,需要寻求辅助生殖技术助孕治疗。本文结合国内外相关文献及病例报道,对卵巢肿瘤患者术后体外受精(IVF)的时机、方案及安全性和有效性等方面进行总结和综述。     

Microbial contamination of embryo cultures in an ART laboratory: sources and management

BACKGROUND: Although rare, microbial contamination of culture dishes occasionally occurs in our IVF/ICSI programme. Despite stringent culture conditions and the use of medium containing penicillin and streptomycin, an increasing number of infections was observed once they were routinely recorded. In this study, 95 cases of contaminated culture dishes were examined, in an attempt to identify possible causes. METHODS: Relevant data of the IVF/ICSI treatment cycles and the micro-organisms isolated from the infected culture dishes were evaluated retrospectively. RESULTS: Infections were observed only in IVF culture dishes and never after applying intra-cytoplasmic sperm injection. Identification of the contaminating micro-organisms showed that infections were mainly caused by Escherichia coli (n = 56; 58.9%) and Candida species (n = 24; 25.3%). Of the E. coli strains isolated, 41 (73.2%) appeared to be resistant to both antibiotics used in the culture medium and 13 (23.2%) appeared to resist either penicillin or streptomycin. Of all bacterial strains isolated, the resistances were 61.4% to both and 30% to one of the antibiotics used. CONCLUSIONS: Applying the ICSI procedure prevents colonization of the culture dishes by micro-organisms. Infections in IVF culture dishes are mainly caused by bacterial strains insensitive to the antibiotics used or due to yeast colonization by Candida species which frequently reside in the vagina.     

Cumulative pregnancy rates after a maximum of nine cycles of modified natural cycle IVF and analysis of patient drop-out: a cohort study

BACKGROUND: In modified natural cycle IVF (MNV-IVF), treatment is aimed at using the one follicle that spontaneously develops to dominance, using a GnRH antagonist together with gonadotrophins in the late follicular phase only. METHODS: In this single-centre cohort study, nine cycles of MNV-IVF were offered to 268 patients. Cumulative pregnancy rates (CPRs) were calculated and drop-out was analysed. The present study is an extension of earlier studies in which three cycles of MNV-IVF were offered to the same patients. RESULTS: A total of 256 patients completed 1048 cycles (4.1 per patient). Embryo transfer rate was 36.5% per started cycle. Ongoing pregnancy rate was 7.9% per started cycle and 20.7% per embryo transfer. Including treatment-independent pregnancies, the observed CPR after up to nine cycles was 44.4% (95% confidence interval 38.3-50.5) per patient. Pregnancy rates per started cycle did not decline in higher cycle numbers (overall 9.9%). Drop-out rates were high (overall 47.8%). We found that cancellation of oocyte retrieval, fertilization failure and failure to reach embryo transfer are repeating phenomena in subsequent cycles and furthermore that these events predispose for drop-out. CONCLUSIONS: CPR after nine cycles of MNV-IVF in this study was 44.4%. Pregnancy rate per cycle did not decline in higher cycle numbers, possibly due to selective drop-out of poor prognosis patients. Due to the low-risk and patient-friendly nature of the MNC protocol, it seems a feasible treatment option for patients requiring IVF.     

A follow-up study of women who donated oocytes to known recipient couples for altruistic reasons

BACKGROUND: Current legislation in Canada allows for only altruistic gamete donation. Limited clinical data are available on the emotional and psychological impact of altruistic oocyte donation on known donors. METHODS: Seventeen women who had donated oocytes to known parties without financial compensation agreed to receive the oocyte donation questionnaire (ODQ) to explore the psychological domains of altruistic oocyte donation. RESULTS: Thirteen ODQ were returned, giving a response rate of 76%. All subjects indicated that they were primarily motivated by a 'desire to give and help' the recipient couple. Most subjects did not find the donation decision difficult but some found the post-donation psychological adjustments challenging. Subjects also indicated that mandatory counselling on the psychological implications of oocyte donation was an important component of cycle preparation. The majority of subjects had disclosed the donation to others and felt that disclosure to the presumptive child was essential. CONCLUSIONS: The findings provide clinical materials for conceptualizing the dynamics entailed by known altruistic oocyte donation, with regards to motivation, relationship implications, donor satisfaction and plans for disclosure. The data support the provision of psycho-social support services to help donors dealing with any residual emotional difficulties regardless of the outcome of oocyte donation.     

Factors determining early pregnancy loss in singleton and multiple implantations

BACKGROUND: The incidence of first trimester pregnancy loss is much lower in IVF twin pregnancies than in IVF singleton pregnancies. The objective of this study was to determine which embryonic and maternal factors contribute to this finding. METHODS: Retrospective data analysis of the outcome of 1593 pregnancies after day 3 double-embryo transfer (DET) after IVF or ICSI treatment. RESULTS: Of 1148 single implantations at 6 weeks, 936 (81.5%) were ongoing pregnancies. Of 445 multiple implantations at 6 weeks, 354 (79.6%) were ongoing multiple pregnancies, 80 (17.9%) were ongoing singleton pregnancies and 11 (2.5%) ended in a spontaneous abortion. Total pregnancy loss was 18.5 and 2.5% (P < 0.001) in singleton and twin gestations, respectively. Loss per gestational sac was 18.5 and 11.46% (P < 0.001), respectively. Determinants contributing to the continuation of gestation beyond 6 weeks were young maternal age, possibility to cryopreserve embryos and short GnRH agonist flare-up stimulation protocol. Whereas factors promoting multiple implantation at 6 weeks of gestation were young maternal age, high cumulative embryo score (CES), male infertility, long stimulation protocol and thick endometrium. CONCLUSIONS: Although multiple implantation at 6 weeks is predominantly determined by (morphological) embryo quality, the continuation of pregnancy beyond 6 weeks becomes more dependent on the combination of genetic and developmental potential of the embryo(s) and an optimal uterine milieu.     

同型半胱氨酸对男性生育力及其IVF妊娠结局影响的研究

目的:研究同型半胱氨酸(Homocysteine,Hcy)对男性生育力及其IVF妊娠结局的影响。方法:收集124对准备行IVF助孕夫妇的男方精液及血液标本。采用酶联免疫吸附试验(ELISA)测定血清与精浆中的Hcy的浓度;分析精浆、血清Hcy浓度与精液参数的关系以及精浆与血清Hcy的关系。结果:按照WHO第五版标准将男性患者分为少精组、弱精组、少弱精组及正常组,其中少精组和少弱精组患者精浆Hcy水平均显著低于正常组(P0.05),两组异常患者间精浆Hcy水平无显著性差异(P0.05)。按IVF助孕后女方妊娠结局成功与否分为两组,两组间精浆Hcy水平无显著性差异(P0.05)。精浆Hcy浓度与精子浓度显著相关(r=0.42,P=0.028),与其他精液参数无相关性;血清Hcy浓度与精液参数无相关性(P0.05)。结论:精浆同型半胱氨酸浓度与精子浓度存在关联性,与其他精液参数无关联性。精浆同型半胱氨酸对男性生育力可能存在一定的影响。     

Innovations ‘Out of Place’: Controversies Over IVF Beginnings in India Between 1978 and 2005

ABSTRACT

In 1978, the year the first in vitro fertilization (IVF) baby was born in the United Kingdom, a research team in Kolkata reported that it too had successfully produced an IVF baby in India. However, the claim was dismissed at the time, because the experiment was conducted outside authorized institutions and recognized centers of innovation—in short, because it was an innovation ‘out of place.’ Tracing controversies over the case between 1978 and 2005, I show the importance of space or place in processes of knowledge production and recognition. Further, I explain the initial repudiation and subsequent partial recognition of the claim through shifts in the landscape of legitimate spaces of innovation. By discussing this specific case of the production of science and technology in the Global South, I challenge conventional narratives of diffusion that are prevalent in studies on the worldwide proliferation of reproductive technologies.     

基础甲状腺功能与IVF-ET妊娠结局的相关性研究

目的研究基础甲状腺功能三项(TSH、FT3、FT4水平)与体外受精-胚胎移植妊娠结局之间的关系。方法以2014年9月至2015年5月在南京大学医学院附属鼓楼医院生殖医学中心行长方案体外受精/卵胞浆内单精子注射-胚胎移植术(IVF/ICSI-ET)并行新鲜胚胎移植的不孕症患者作为研究对象。于IVF前月经第2~4天空腹留血,检测基础甲状腺功能三项:促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)。纳入甲状腺功能三项均正常的患者486例,分析基础甲状腺功能与IVF/ICSI妊娠结局的关系。结果 (1)486例患者中临床妊娠305例,活产249例,早期自然流产23例;(2)临床妊娠组与未妊娠组比较,TSH、FT3、FT4水平均无统计学差异(P0.05),临床妊娠组女方年龄小[(29.4±3.9)vs.(30.7±4.3)岁,P=0.001)]、子宫内膜厚[(11.0±2.2)mm vs.(9.9±1.9)mm,P0.001)];(3)活产组与早期自然流产组相比,基础TSH、FT3、FT4差异均无统计学意义(P0.05);(4)基础TSH≥2.5mIU/L的患者与TSH2.5mIU/L者的临床妊娠率、活产率、早期自然流产率和新生儿出生体重均无统计学差异(P0.05)。结论基础甲状腺功能三项如在正常范围不影响IVF结局,IVF前TSH≥2.5mIU/L但4.2mIU/L时不增加早期自然流产率,也不影响新生儿出生体重。