ABO血型系统对新鲜周期胚胎移植妊娠结局的影响

目的:研究接受新鲜周期胚胎移植的体外受精/卵胞浆内单精子注射(IVF/ICSI)助孕治疗的卵巢功能正常患者的ABO血型与妊娠结局之间的关系。方法:回顾分析2015年5月1日至2017年5月1日于郑州大学第三附属医院生殖中心行新鲜胚胎移植的2323例IVF/ICSI周期,根据血型分为A组(n=637)、B组(n=803)、O组(n=664)、AB组(n=219)。比较各组的一般情况及妊娠结局。应用二元逻辑回归分析患者血型与活产及临床妊娠结果的关系,同时控制混杂因素,估算优势比(OR)及95%置信区间(95%CI)。结果:ABO血型组间的临床妊娠率、活产率、早产率、流产率、OHSS发生率、孕龄及新生儿出生体重比较,差异均无统计学意义(P0.05)。年龄、BMI是临床妊娠的危险因素,OR(95%CI)分别为1.477(1.222～1.785)、1.255(1.057～1.490)。年龄是活产的危险因素,Gn总剂量、Gn天数是活产的保护因素,OR(95%CI)分别为1.380(1.145～1.662)、0.808(0.670～0.976)、0.763(0.614～0.946)。结论:卵巢功能正常接受新鲜周期胚胎移植的IVF/ICSI助孕患者的ABO血型与妊娠结局无关。考虑如年龄、BMI、卵巢刺激持续时间、促性腺激素剂量和移植日子宫内膜厚度等多种混杂因素后,结果不变。这些结果需更大规模的队列研究或前瞻性研究验证。     

Bed rest following embryo transfer might negatively affect the outcome of IVF/ICSI: a systematic review and meta-analysis

The majority of patients undergoing in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) treatment will reach the stage of embryo transfer (ET), but only a small proportion of transferred embryos implant. Bed rest following ET has been recommended as a way to prevent embryo expulsion by gravity. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) published prior to May 2014 reporting the effect of bed rest following ET, and irrespective of language, country of origin, blinding or sample size. Four RCTs, including 757 women met the inclusion criteria. Bed rest following ET did not improve clinical pregnancy and live birth rates, but reduced the implantation rate. The quality of the trials included was moderate because of attrition bias and possible reporting bias. The findings of this systematic review and meta-analysis are concordant with previously published literature and suggest that bed rest is not beneficial following ET. Moreover, it might negatively affect the outcome of IVF/ICSI cycles via stress/anxiety mechanisms.     

The effect of endometrial thickness on the day of hCG administration on pregnancy outcome in the first fresh IVF/ICSI cycle

The aim of this study was to investigate the effect of endometrial thickness (EMT) on human chorionic gonadotropin (hCG) day on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcome. A retrospective study was conducted on the clinical data of 756 patients in their first fresh IVF/ICSI cycle at the Wuxi Maternity and Child Health Hospital. Compared with the pregnancy failure group, the clinical pregnancy group had more transferable embryos and good-quality embryos and had a thicker endometrium (p?<?0.05). The endometrial pattern was not significantly different between the two groups. EMT was found to be an independent prognostic factor for clinical pregnancy (adjusted OR?=?1.25, 95% CI: 1.15–1.36, p?<?0.01). Seven hundred and fifty-six cycles were categorized into three groups upon EMT on the hCG day: group 1 (EMT??14?mm). Group1 had significantly lower clinical pregnancy, embryo implantation and live birth rates compared with group 2 and 3 (p?<?0.01), while there was no significant difference in either spontaneous abortion or multiple-birth rate among these three groups. It was concluded that EMT on the hCG day was associated with pregnancy outcome in the first fresh IVF/ICSI cycle. A higher clinical pregnancy rate could be achieved when EMT?≥?8?mm, and no adverse pregnancy outcome was observed when EMT?>?14?mm.     

Both high and low HCG day progesterone concentrations negatively affect live birth rates in IVF/ICSI cycles

Research questionCan previous reports of a decreased probability of success in stimulated IVF cycles with premature rise of progesterone, as determined by progesterone concentration on HCG day (PHCG), be confirmed?DesignRetrospective, observational, single-centre cohort study conducted on 5447 IVF and intracytoplasmic (ICSI) cycles carried out among 2192 patients between 2009 and 2015, with conventional ovarian stimulation. This large database was used to develop a non-linear mixed prognosis model of live birth rate (LBR) incorporating PHCG as a predictor.ResultsIn addition to known predictors (age, body mass index, anti-Müllerian hormone, type of infertility), PHCG was associated with a linear effect (OR 0.78 per Log[PHCG]ng/ml, 95% CI 0.611 to 0.997, P = 0.047) combined with a strong quadratic effect (OR 0.585 per Log²(PHCG)ng/ml, 95% CI 0.444 to 0.775, P < 0.001) resulting into a parabolic reverse-U curve. A significant interaction (P = 0.038) was found between PHCG and number of oocytes if three or less, but the effect of PHCG remains modest. For higher oocyte numbers, LBR rapidly increases with number of retrieved oocytes; however, LBR becomes more sensitive to PHCG as the number of oocytes increases. Higher live birth prognoses occur for optimal PHCG but are sharply reduced for lower or higher PHCG.ConclusionsEvidence is provided of an important negative effect of PHCG at lower and higher values, independent of oocyte number, thus defining appropriate ranges for fresh embryo transfer or freeze-all strategy. In poor responders, premature progesterone rise may be ignored, thus avoiding unnecessary cancellations or embryo freezing. Conversely, in higher responders, the negative effect of progesterone elevation is more pronounced, suggesting that freeze-all policy should be applied more widely.     

Antimullerian hormone (AMH) level and IVF/ICSI cycle outcome in expected poor responders

Objective

to study AMH level effect on IVF/ICSI cycle outcome in expected poor responders undergoing ART.

Prediction of IVF/ICSI outcome based on the follicular output rate

This study assessed the true accuracy of follicular output rate (FORT) as a prognostic indicator of response to FSH and reproductive competence after IVF/intracytoplasmic sperm injection. A total of 1643 cycles, including 140 polycystic ovary syndrome (PCOS) patients who underwent ovarian stimulation, were studied. FORT was calculated as the ratio of preovulatory follicle count on the day of stimulation × 100/small antral follicle count (3–10 mm in diameter) at baseline. Low, medium and high FORT groups were defined according to tertile values. Among 1503 non-PCOS cycles, numbers of retrieved oocytes and of all embryos that could be transferred, as well as rates of good-quality embryos, embryo implantations and clinical pregnancies, progressively increased with FORT. In PCOS patients, FORT were significantly lower in patients who achieved clinical pregnancy compared with those who did not (0.56 ± 0.21 versus 0.66 ± 0.29, P = 0.031). Fertilization and good-quality embryo rates were significantly higher with medium FORT than low and high FORT (P = 0.001 and P = 0.047, respectively). Medium FORT in PCOS patients and high FORT in non-PCOS patients may predict better outcomes for IVF/ICSI.In the present study, we aimed to assess the true accuracy of the follicular output rate (FORT) as a prognostic indicator of the response to FSH and reproductive competence after IVF/intracytoplasmic sperm injection (ICSI). A total of 1643 IVF/ICSI cycles, including 140 polycystic ovary syndrome (PCOS) patients who underwent ovarian stimulation, were studied. FORT was calculated as the ratio of the preovulatory follicle count (PFC) on the day of human chorionic gonadotrophin stimulation × 100/small antral follicle count (AFC; 3–10 mm in diameter) at baseline. Low, medium and high FORT groups were defined according to the tertile values. Among 1503 non-PCOS cycles, the numbers of retrieved oocytes and of all embryos that could be transferred, as well as the rates of good-quality embryos, embryo implantations and clinical pregnancies, progressively increased from the lower to higher FORT groups. In PCOS patients, FORT was significantly lower in the patients who achieved clinical pregnancy compared with those who did not (0.56 ± 0.21 versus 0.66 ± 0.29, P < 0.05). Fertilization and good-quality embryo rates were significantly higher in the medium FORT group compared with the low and high FORT groups. The data from the present study suggest that medium FORT values in PCOS patients and high FORT values in non-PCOS patients may predict better outcomes for IVF/ICSI.     

Injection of embryo culture supernatant to the endometrial cavity does not affect outcomes in IVF/ICSI or oocyte donation cycles: a randomized clinical trial

Objective

To evaluate whether intrauterine injection of embryo culture supernatant before embryo transfer has any impact on pregnancy and implantation rates.

Study design

A total of 400 cycles, of which 200 IVF/ICSI and 200 oocyte donor (OD), were randomly assigned to have their uterine cavity injected (group I) or not (group II). Primary endpoints to be studied were pregnancy and implantation rates.

Results

Clinical pregnancy rate per transfer (47.87%, 90/188 versus 48.45%, 94/194) based on transvaginal scan findings at 7 weeks of gestation and implantation rate (25.6% versus 26.5%) were similar in the two groups. The day of embryo transfer, day 3 or day 5, did not affect the final outcome.

Conclusion

Injection of embryo culture supernatant into the uterine cavity, 30 min before the embryo transfer on either day 3 or 5, neither improves nor adversely affects the pregnancy rate in IVF/ICSI or oocyte donation cycles.     

Adding serum estradiol measurements to ultrasound monitoring does not change the yield of mature oocytes in IVF/ICSI

In a non-randomized, comparative prospective study (416 patients) we compared the outcome of IVF/ICSI in two parallel control groups: one in which patients were followed up using combined monitoring (ultrasound plus serum estradiol monitoring, the UHM group) and one in which only ultrasound monitoring was used (the UM group). This study has taken the number of mature oocytes at the moment of egg retrieval as its primary end variable. After adjustment for age, gravidity, antagonist protocol, AMH and infertility diagnosis, the average difference in number of mature oocytes between the UHM group and the UM group was ?0.4 (95% CI: ?1.7 to 1.0), which met our definition of clinical equivalence (95% CI for the adjusted mean difference between ?2 and 2). Larger studies are still needed to evaluate the differences in the live birth rates per cycle and to further confirm that blood sampling definitively has no added value in monitoring ovarian stimulation for IVF/ICSI.     

The ReceptIVFity cohort study protocol to validate the urogenital microbiome as predictor for IVF or IVF/ICSI outcome

Background

During the last decade, research has shown that besides the known predictive factors, such as duration of subfertility, a women’s age, the body mass index, also the microbiome might affect fertility. Micro-organisms together with their genetic information and the milieu in which they interact are called the microbiome. Studies have shown that the presence of certain microbiota during assisted reproductive technology (ART) has a positive impact on the outcome. However, the potential role of using the microbiome as a predictor for outcome of ART has not yet been investigated.

Methods

In a prospective study, 300 women of reproductive age and with an indication for in-vitro Fertilization (IVF) with or without Intra Cytoplasmic Sperm Injection (ICSI) treatment will be included. Prior to the IVF or IVF-ICSI treatment, these women provided a midstream urine sample and a vaginal swab. The composition of the urinary and vaginal microbiome will be analysed with both Next Generation Sequencing and the IS-pro technique. The endpoints of the study are pregnancy achieved after fresh embryo transfer (ET) and within the subsequent year after inclusion. External validation of the findings will take place in an additional cohort of 50 women with an IVF or IVF-ICSI indication.

Discussion

In the proposed study, the predictive accuracy of the composition of the urinary and vaginal microbiome for IVF or IVF-ICSI outcome will be only validated for fresh ET. Follow-up has to show whether the predictive accuracy will be similar during the consecutive frozen ET’s as part of the IVF or IVF-ICSI treatment or for subsequent stimulated or natural cycles. In addition, external validation will take place in another cohort and hospital. Predictive knowledge of the microbiome profile may enable couples to make a more substantiated decision on whether to continue treatment or not. Hence, the unnecessary physical and emotional burden of a failed IVF or IVF-ICSI treatment can be avoided.

Trial registration

ISRCTN ISRCTN83157250. Registered 17 August 2018. Retrospectively registered.

     

Y chromosome AZFc microdeletion may not affect the outcomes of ICSI for infertile males with fresh ejaculated sperm

Purpose

To explore whether the presence of a Y chromosome AZFc microdeletion confers any adverse effect on the outcomes of intracytoplasmic sperm injection (ICSI) with fresh ejaculated sperm.

Methods

A total of 143 oligozoospermia patients with Y chromosome AZFc microdeletion in ICSI cycles in a five-year period were studied. Infertile men with normal Y chromosome in ICSI at the same time-frame were used as controls matched to the study group for age of female, female’s body mass index, male’s age, infertility duration and number of oocytes retrieved. Retrospective case–control study was used.

Results

There were no significant differences between groups in clinical outcomes of endometrial thickness, transferred embryos, good embryo rates, implantation rates, biochemical pregnancy rates, clinical pregnancy rates, ectopic pregnancy rates, miscarriage rates, preterm birth rates, the ratio of male and female babies, newborn body height, newborn weight, low birth weight and birth defects (P > 0.05). Patients with Y chromosome AZFc microdeletion had a lower fertilization rate (61.8 % vs. 67.8 %, P < 0.05) and higher cleaved embryo rate (94.0 % vs. 88.1 %, P < 0.05).

Conclusions

ICSI clinical outcomes for oligozoospermic patients with Y chromosome AZFc microdeletion are basically comparable to that of infertile patients with normal Y chromosomes. The results of ICSI were not affected by the AZFc deletion. Preimplantation genetic diagnosis (PGD) before ICSI for Y chromosome AZFc microdeletion may not be a justifiable regular procedure if the couples didn’t care the vertical transmission of Y chromosome deletion.     

Obstetric outcome and incidence of congenital anomalies in 2351 IVF/ICSI babies

Purpose

The aim of this study was to provide a comprehensive follow-up of fetal and perinatal outcome and the incidence of congenital anomalies in babies born after fresh embryo transfers compared to those conceived spontaneously in infertile couples.

Methods

Retrospective comparative analysis of all clinical pregnancies from fresh cleavage-stage embryo transfer cycles (IVF and ICSI) compared with infertile patients who conceived spontaneously in the same time period (control). Congenital anomalies were classified following the European Surveillance of Congenital Anomalies (EUROCAT) classification.

Results

A total of 2414 assisted reproductive technology (ART) pregnancies were compared to 582 spontaneous conceptions in the control infertile group representing 2306 deliveries. No significant differences were found in pregnancy outcome between the two groups (delivery rate, abortion rate, ectopic pregnancies, medical abortions for fetal anomalies, single and twins mean gestational age, and weight at delivery). A significant difference (p?<?0.001) was found in the twin (21.3 vs 2.3 %) and triplet rates (2.3 vs 0 %). A total of 2351 babies were delivered in the ART group and 449 in the control group. A total of 90 babies (3.8 %) were diagnosed with a major congenital anomaly in the ART group and 15 (3.3 %) in the control group (p?=?ns). The overall rate of major congenital anomalies (105/2800) in ART and spontaneous pregnancies in infertile couples was significantly higher when compared to the EUROCAT 2.0 versus 3.75 % (p?=?0.0002).

Discussion

Babies born after ART treatments and from spontaneous conception in infertile couples had rates of congenital anomalies higher than those recorded by the EUROCAT. However, the rates of anomalies were not different within the infertile population whether conceived by ART or spontaneously. These data suggest that the diagnosis of infertility in itself is the common denominator for the increase in the rates of anomalies seen in both ART and spontaneous conceptions.

     

Influence of ovarian stimulation for IVF/ICSI on the antioxidant defence system and relationship to outcome

Ovarian stimulation is used with IVF/intracytoplasmic sperm injection (ICSI) cycles to obtain multiple oocytes and improve pregnancy rates; however, it also induces perturbation in the oxidant–antioxidant balance leading to oxidation stress. The present study monitored the plasma antioxidant status in women undergoing a long agonist protocol of ovarian stimulation at three different time points: at baseline (T0), after pituitary suppression (T1) and on the day of oocyte retrieval (T2). The antioxidant composition of follicular fluid samples collected on T2 was also evaluated. Significant decreases (P < 0.05) of plasma vitamin C, vitamin E and carotenoids were found between T1 and T2 but not between T0 and T1. At T2, high plasma vitamin E was associated with high numbers of total and mature oocytes retrieved per patient, which, in turn, were favourable for achieving pregnancy. Accordingly, women who became pregnant presented higher vitamin E concentrations both in plasma and FF than those who did not. In conclusion, this study confirmed the occurrence of significant modifications of the plasma antioxidant profile during ovarian stimulation with gonadotrophins; at the same time, it was found that both systemic and follicular antioxidant status may be related to IVF/ICSI outcome.     

Long-term cryostorage does not adversely affect the outcome of oocyte thawing cycles

This multi-centre study evaluated systematically the influence of the duration of cryostorage on the outcome of thawing cycles when using slow-frozen oocytes. The thawing cycles were retrospectively divided into three main groups based on cryostorage duration: group A, 1–3 months; group B, 4–6 months; and group C, 7–48 months. Group C was subsequently divided into three subgroups: group C1, 7–9 months; group C2, 10–12 months; and group C3, 13–48 months. Main outcome measures observed were oocyte survival after thawing, fertilization, cleavage; embryo quality and development, implantation, and birth. No significant differences in main outcome measures were observed between all the groups studied. In conclusion, human oocytes can be safely cryostored for several years. This finding could encourage the wider use of oocyte cryopreservation as a clinical procedure in assisted reproduction.     

The origin of spermatozoa does not affect intracytoplasmic sperm injection outcome

OBJECTIVE: To assess whether the origin of spermatozoa, ejaculate or testicular, affects intracytoplasmic sperm injection (ICSI) outcome. STUDY DESIGN: Retrospective study of 890 consecutive first ICSI and embryo transfer cycles done for male infertility. The ICSI outcome of ejaculated spermatozoa (n=780) and testicular spermatozoa retrieved from patients with obstructive azoospermia (n=43), non-obstructive azoospermia (n=53) and severe oligoasthenoteratozoospermia (n=14) were compared by using chi-square test, independent t-test and ANOVA with Bonferroni test. RESULTS: All azoospermic males had a diagnostic testicular biopsy at least 6 months before the ICSI procedure. Spermatozoa were successfully retrieved in all 43 patients with obstructive azoospermia and in 72.6% of 73 non-obstructive cases. The cycle characteristics of the four groups were similar apart from a younger mean female age in the non-obstructive azoospermia group when compared with the ejaculated spermatozoa group. The fertilization, implantation and clinical pregnancy rates were comparable among the four groups. CONCLUSION: Testicular spermatozoa recovered from patients with obstructive and all types of non-obstructive azoospermia were as much as effective as ejaculated spermatozoa in ICSI.     

Route of progesterone administration for luteal phase support may affect outcome of controlled ovarian hyperstimulation for IVF with ICSI using GnRH antagonist

Purpose

This study evaluated the impact of route of progesterone administration as luteal phase support on the outcome of assisted conception cycles.

Methods

Intramuscular progesterone in oil (IMP) at 100 mg daily was administered to 903 women following oocyte retrieval whereas vaginal progesterone gel (VMP) at 90 mg was administered twice daily to 1,110 women. Retrospective analysis was performed according to the type of GnRH analogue used. Implantation (IR), clinical pregnancy (CPR) and biochemical pregnancy rates (BPR) were main outcomes.

Results

In GnRH agonist cycles, neither IR, CPR or BPR differed according to the route of progesterone. However, in GnRH antagonist cycles, IR and CPR were significantly lower in VMP group compared to IMP group. BPR also was significantly higher in VMP group compared to IMP group.

Conclusion

Our results suggest that route of progesterone administration for luteal phase support can be an important prognostic factor according to the type of GnRH analogue used for controlled ovarian hyperstimulation.     

The influence of early cleavage on embryo developmental potential and IVF/ICSI outcome

Purpose  

To observe whether early cleavage can be a predictor of embryo developmental potential, pregnancy and implantation rates.     

PGT for aneuploidy does not affect three-cycle cumulative IVF discontinuation rate in women of advanced maternal age

Research questionDoes preimplantation genetic testing for aneuploidy (PGT-A) influence the discontinuation rate in women with advanced maternal age (AMA) undergoing IVF?DesignRetrospective longitudinal cohort study carried out at a single IVF clinic in Turkey. In total, 401 consecutive AMA cases were included. Discontinuation rates of pre-intervention (conventional IVF; June 2013 to October 2014; 203 couples; 270 cycles) and post-intervention (PGT-A; April 2015 to June 2016; 198 couples; 285 cycles) periods were compared. To delineate the reason for discontinuation, a telephone survey was conducted. Primary outcome measure was cumulative discontinuation rate before completing three cycles of IVF treatment without achieving an ongoing pregnancy.ResultsThe discontinuation rates after the first and second failed cycles were comparable between the two arms as were the cumulative discontinuation rates before completing three cycles. The cumulative ongoing pregnancy rate per embryo transfer was significantly higher in the PGT-A arm (43.2% versus 16.8%; P < 0.001). The cumulative ongoing pregnancy rate per patient was comparable between the two arms (20.7% versus 16.3%, respectively). Female age was the only significant contributor to treatment discontinuation (hazard ratio [HR] 1.07; 95% CI 1.09 to 1.13). Of the 296 couples discontinuing treatment in both arms, 179 (179/296 [60.5%]) participated in the survey; overall, psychological burden was the main reason for treatment discontinuation (37/179 [20.7%]).ConclusionsAbout 90% of AMA cases not achieving an ongoing pregnancy discontinue IVF treatment before completing three cycles. Discontinuation rate is not reduced by carrying out PGT-A. Female ageing is the only significant contributor, with a hazard of discontinuing further IVF treatment of 7% with female ageing of 1-year.     

The influence of the type of embryo culture media on the outcome of IVF/ICSI cycles

ObjectiveEmbryo culture media are important factors in IVF, which can significantly influence clinical outcome of IVF/ICSI cycles. Despite this, it is still not completely clear which formulation is most optimal and whether sequential or continuous media should be favored.Materials and methodsThis study retrospectively analyzed the outcome of IVF/ICSI cycles with regard to different types of culture media used to culture embryos, namely sequential and two types of single step continuous embryo culture media.ResultsIf the data were combined for both types of single step continuous embryo culture media the only significant difference we observed was the proportion of poor quality embryos on day 3, which was significantly higher (16.9% vs. 22.5%; P = 0.017) in the sequential media. The pregnancy (55.1% vs. 40.5%; P = 0.113) and live birth rates (42.9% vs. 33.8%; P = 0.308) were lower in continuous media, although the difference was not statistically significant. Furthermore, the blastocyst rate (sequential vs. continuous; 47.4% vs. 47.3%; P = 1), and birthweight (3280 ± 630g vs. 3272 ± 575g; P = 0.96) did not significantly differ regardless of the medium used to culture embryos. Additional comparison of each type of continuous medium to sequential media revealed that the difference in the quality of cleavage stage embryos for combined data of both continuous culture media may be derived from the group of cycles were SAGE 1-Step was used to culture embryos.ConclusionThese results therefore indicate that continuous media can be equivalent to sequential media and could help lower the workload in busy IVF labs without impairing the clinical results. Although, caution is needed because this study is limited by its retrospective design. To confirm the results, especially in terms of live birth rates and perinatal outcome, a prospective study is needed with a higher number of included couples.     

IVF/ICSI周期中不同移植方案的临床结局及经济学分析

目的:探讨IVF/ICSI周期中第三天可利用胚胎为5枚以上的患者选择不同移植方案的临床结局及经济学评价。方法:选取2014年1月至2015年12月于郑州大学第三附属医院生殖医学中心行IVF/ICSI-ET治疗不孕症的1400例周期,按移植方案分为3组:移植D3胚胎(A组,1109个周期),非选择性囊胚移植组(B组,160个周期),选择性(单)囊胚移植组(C组,131个周期)。分析各组的临床结局和经济学成本。结果:A组患者的获卵数和种植率均明显低于B组和C组,差异均有统计学意义(P0.05);3组患者的2PN受精率、卵裂率、可移植胚胎率、优质胚胎率、临床妊娠率和流产率比较,差异均无统计学意义(P0.05)。A组患者的多胎率明显高于B组和C组(P均=0.000),且B组明显高于C组(P=0.000)。C组患者移植的成本效果比最小。结论:3组移植方案的临床妊娠率相似;选择性单囊胚移植明显提高胚胎种植率,降低多胎率,治疗成本效果比最小,是相对最佳的移植方案。