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.     

Cannulation of a resistant internal os with the malleable outer sheath of a coaxial soft embryo transfer catheter does not affect in vitro fertilization-embryo transfer outcome

OBJECTIVE: To assess the impact of cannulation of a resistant cervical os with the outer malleable sheath of a double-lumen, soft ET catheter on IVF-ET outcomes. DESIGN: Retrospective cohort study. SETTING: University-based IVF center. PATIENT(S): One hundred forty-two patients undergoing 142 ETs. INTERVENTION(S): Trial ultrasound-guided ET at all transfers, leaving the malleable outer sheath in situ when the soft inner catheter could not negotiate the internal os. MAIN OUTCOME MEASURE(S): Implantation rate and clinical pregnancy rate. RESULT(S): In 102 ETs (71.8%), the soft inner sheath easily negotiated the internal os (group 1). Forty ETs (28.2%) required cannulation of resistant internal ora with the outer sheath of the trial catheter (group 2). Implantation rates (35% vs. 32% in groups 1 and 2, respectively) and clinical pregnancy rates (50% vs. 45%) were not significantly different between groups. Blood was present on the transfer catheter after ET more frequently in group 2 than in group 1 (55% vs. 15%); however, neither the implantation rate nor the clinical pregnancy rate were affected by the presence of blood. CONCLUSION(S): Cannulation of a resistant internal os by the malleable outer sheath and blood on the transfer catheter after ET do not have an adverse effect on implantation rate or clinical pregnancy rate.     

Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization

Objective: To evaluate the effect of prednisolone plus low-dose aspirin (PSL/LDA) in women with autoimmune conditions who were enrolled in an IVF-ET program.

Design: A retrospective clinical study.

Setting: In vitro fertilization unit, Niigata University Hospital, Niigata, Japan.

Patient(s): Three hundred seven women who underwent IVF-ET between January 1996 and December 1997.

Intervention(s): Prednisolone (10 mg/d) and aspirin (81 mg/d) were administered to the women with autoantibodies who chose to participate.

Main Outcome Measure(s): Pregnancy and implantation rates with IVF-ET.

Result(s): Women undergoing IVF who had positive antinuclear antibodies, with or without antiphospholipid antibodies, had significantly lower pregnancy and implantation rates than did women without autoantibodies (14.8% versus 21.7% and 6.8% versus 10.4%, respectively). The administration of PSL/LDA to women with antinuclear antibodies significantly improved the outcome of IVF-ET (40.6% pregnancy rate and 20.3% implantation rate).

Conclusion(s): A high proportion of women who are undergoing IVF-ET have autoantibodies, which are associated with poor IVF outcomes. The administration of PSL/LDA to these women may improve their implantation rate.     

Influence of the morphological aspect of embryos obtained by in vitro fertilization on their implantation rate

In a series of 500 transfers of embryos obtained by in vitro fertilization, we examined the implantation rate of 1356 embryos transferred in utero. The average implantation rate per embryo was 15.1% and remained relatively constant, regardless of the number of transferred embryos per patient. The implantation rate per embryo, in relation to its morphology, was clearly lower when irregular blastomeres and fragments were present in the perivitelline area. Other embryos, regardless of their morphology, had an identical development potential. Analysis of the results of this series demonstrates the difficulty of deter-mining the development potential of all the embryos on the basis of morphological criteria.     

全部胚胎冷冻保存在卵巢低反应患者微刺激方案IVF-ET中的应用

目的:探讨全部胚胎冷冻保存对卵巢低反应患者微刺激方案助孕结局的影响。方法:回顾性分析微刺激方案IVF-ET共483个周期,根据胚胎移植时机不同分为A组(新鲜胚胎移植组,275个周期)和B组[全部胚胎冷冻保存首次冷冻胚胎复苏移植术(FET)组,208个周期],比较组间患者的年龄、基础FSH、不孕年限、扳机日优势卵泡数目、内膜厚度、获卵数、可利用胚胎数及临床妊娠率、胚胎种植率、流产率。结果:A组扳机日内膜厚度和获卵数高于B组,差异有统计学意义(P0.05),A组的临床妊娠率、胚胎种植率低于B组,差异有统计学意义(P0.05),患者的年龄、基础FSH、Gn总量、扳机日优势卵泡数、扳机日雌二醇(E2)和孕酮(P)值、可利用胚胎数、移植周期内膜厚度、移植胚胎数、流产率组间均无统计学差异(P0.05)。结论:对于使用微刺激方案助孕的卵巢低反应患者,全部胚胎冻存择期进行FET可以改善其助孕结局,是一种值得临床推广的助孕策略。     

Elevated serum progesterone level on the day of human chorionic gonadotropin administration does not adversely affect implantation rates after intracytoplasmic sperm injection and embryo transfer

Objective: To evaluate the association between serum P levels on the day of hCG administration and the outcome of intracytoplasmic sperm injection (ICSI).

Design: Retrospective case study.

Setting: Assisted reproduction unit of a tertiary care private hospital.

Patient(s): Nine hundred eleven ICSI cycles that proceeded to ET were studied.

Intervention(s): The decision to administer hCG was based on serum E₂ levels and follicle size. Serum P was measured from frozen sera obtained on the day of hCG administration. Cycles were stratified according to serum P levels of <0.9 ng/mL (n = 298) or ≥0.9 ng/mL (n = 613). This cutoff level was selected because it yielded the highest sensitivity and specificity according to a receiver operator characteristic curve.

Main Outcome Measure(s): Implantation and clinical pregnancy rates.

Result(s): In cycles with high serum P levels, more oocytes were retrieved and more embryos were available for transfer. Clinical pregnancy rates per ET in the low and high P groups were 36.9% and 45.4%, respectively (P<.05). The implantation rate per embryo was similar in the two groups (14.9% and 16.4%, respectively, in cycles with P levels <0.9 vs ≥0.9 ng/mL). Abortion rates were 22.7 and 25.8%, respectively (P>.05).

Conclusion(s): Our data showed no adverse effect of high serum P levels on the day of hCG administration on implantation rates after ICSI and ET.     

Air in the transfer catheter does not affect the success of embryo transfer

Objective

To investigate the effect on embryo transfer (ET) success of air loaded into the transfer catheter to bracket the embryo-containing medium.

Design

Prospective, randomized study.

Setting

University teaching hospital.

Patient(s)

One hundred two consecutive patients undergoing ET after IVF.

Intervention(s)

In group 1 (n = 52), embryos were loaded as follows: 200 μL of air in the syringe, 100-125 μL of air in the proximal part of the catheter, 20-25 μL of medium containing the embryos to be transferred, and 10 μL of air at the tip of the catheter. In group 2 (n = 50), the syringe and the entire catheter were filled with medium and the embryo-containing medium (20-25 μL) was aspirated without being bracketed by air spaces.

Main outcome measure(s)

Implantation and pregnancy rates.

Result(s)

No differences were found between groups 1 and 2 with respect to implantation and pregnancy rates.

Conclusion(s)

The air loaded into the transfer catheter to bracket the embryo-containing medium has no negative effect on ET success.     

Detection of antisperm antibodies in seminal plasma by flow cytometry: comparison with the indirect immunobead binding test

Objective: To compare flow cytometry with the established indirect immunobead binding test (IBT) for the detection of antisperm antibodies in seminal plasma.

Design: A prospective, comparative study.

Setting: University-based and rology unit.

Patient(s): One hundred and fifty-eight men with suspected male factor subfertility.

Intervention(s): Seminal plasma samples were incubated with antisperm antibody-negative donor sperm. Surface-bound antibody was detected with fluorescence-labeled antihuman antibody in the flow cytometry assay or with immunobead-labeled antihuman antibody in the IBT.

Main Outcome Measure(s): The percentage of sperm that tested positive for surface-bound antibody was determined in the two assays. Seminal plasma was antisperm antibody-positive when ≥20% of the sperm were antibody-bound, and clinically significant levels were present when ≥50% of the sperm were antibody-bound.

Result(s): Of 71 samples that were negative by the IMT, 66 (93%) also were negative by flow cytometry. Of 63 samples that had ≥50% immunobead binding, 55 had equivalent results by flow cytometry. Overall statistical analysis showed a good correlation between the two assays.

Conclusion(s): There is a good correlation between the indirect IBT and indirect flow cytometry for the detection of antisperm antibodies in seminal plasma.     

薄型子宫内膜新鲜胚胎和冻融胚胎移植妊娠结局比较

目的探讨在薄型子宫内膜患者中新鲜胚胎移植与冻融胚胎移植(FET)妊娠结局的差异。方法回顾性分析接受体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)治疗采用长方案胚胎移植h CG注射日与冻融周期胚胎移植内膜转化日的内膜厚度≤7 mm的患者共592个周期的临床资料。将移植周期按胚胎是否冻融分为新鲜胚胎移植组(n=173)和FET组(n=419)。比较组间的胚胎种植率、临床妊娠率、流产率、多胎率和异位妊娠率有无差异。结果新鲜胚胎移植组患者平均移植胚胎(2.1±0.4)枚,与FET组患者平均移植胚胎(2.1±0.5)枚比较,组间有统计学差异(P0.05);按照移植胚胎数分为3个亚组,新鲜胚胎移植组1枚胚胎者,妊娠率为7.7%,2枚者为30.2%,3枚者为23.8%;FET组1枚胚胎者15.6%,2枚者为34.9%,3枚者为41.6%,新鲜胚胎移植组与FET组间差异均无统计学意义(P0.05)。组间着床率、流产率、异位妊娠率等结果也均无统计学差异(P0.05)。移植3枚胚胎新鲜组多胎率(80.0%)高于FET组(29.7%)(P0.05)。新鲜胚胎移植组多胎率3个亚组间有统计学差异(P0.05),FET组妊娠率和流产率3个亚组间均有统计学差异(P0.05)。将移植胚胎数作为协变量,纳入Logistics回归模型对结果变量进行分析,说明周期类型与临床妊娠率间无显著相关性(OR=0.726,95%CI=0.504~1.104)。结论子宫内膜厚度≤7 mm的薄型内膜患者新鲜胚胎移植和FET妊娠结局相似,选择新鲜周期移植不影响妊娠结局并可缩短治疗周期,降低总费用。     

Passive immunization with antisperm monoclonal antibody ZAP-7 increases preimplantation embryo mortality in the mouse

Objective: To evaluate the effect of VIC-1 and ZAP-7 antihuman sperm monoclonal antibodies on in vivo fertility in the mouse.

Design: A randomized blinded study using a mouse model.

Setting: University-based laboratory.

Animals: B6CBAF1 mice (n = 6 per experimental group).

Intervention(s): Antisperm antibodies were administered intravaginally to female mice before mating. Control mice received no treatment, saline, or nonspecific antibodies. Number and viability of preimplantation embryos were determined by microscopic observation. Mouse sperm, oocytes, and normal preimplantation embryos were used in indirect immunofluorescence assays with antisperm antibodies. The effect of antibody treatment on sperm motility and vitality was evaluated.

Main Outcome Measure(s): Antigen expression, sperm motility and vitality, number and viability of embryos.

Result(s): ZAP-7 antibody recognizes a sperm antigen expressed in zygotes and early preimplantation embryos. Passive immunization with ZAP-7 increases embryo mortality significantly (more than 40% above controls). Passive immunization with VIC-1 has no deleterious effect.

Conclusion(s): ZAP-7 monoclonal antibody disrupts fertilization and embryogenesis in the mouse.     

Cumulative live birth rate of advanced-age women more than 40 with or without poor ovarian response

Objective

The aim of this study was to investigate cumulative live birth rate (CLBR) per oocyte retrieval cycle and per patient in women over 40 years old undergoing IVF/ICSI treatments, stratified for age, ovarian response and oocyte retrieval cycle number.

Increased endometrial thickness on the day of human chorionic gonadotropin injection does not adversely affect pregnancy or implantation rates following in vitro fertilization-embryo transfer

OBJECTIVES: To investigate the controversy whether an increased endometrial thickness has an effect on pregnancy, implantation, or abortion rates in in vitro fertilization-embryo transfer (IVF-ET) cycles. DESIGN: Retrospective analysis. SETTING: A university-based IVF center. PATIENT(S): Five hundred seventy women under the age of 40. INTERVENTION(S): Measurements of endometrial thickness on day of human chorionic gonadotropin (hCG) administration. Cycles were compared by endometrial thickness of 14 mm in 60 women. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and abortion rates. RESULT(S): Implantation, pregnancy, and abortion rates were similar in each group. In cycles where the endometrial thickness was 14 mm. CONCLUSION(S): No adverse effects of a thickened endometrium were demonstrated on implantation, pregnancy, or abortion rates in the first IVF-ET cycle. These findings fail to corroborate with those of Weissman et al. and support those of Yakin et al.     

Assessment of leukemia inhibitory factor levels by uterine flushing at the time of egg retrieval does not adversely affect pregnancy rates with in vitro fertilization

OBJECTIVE: To assess intrauterine levels of leukemia inhibitory factor (LIF) by uterine flushing at the time of egg retrieval and to confirm that the procedure has no detrimental effect on pregnancy rates. DESIGN: Prospective study. SETTING: Assisted reproductive unit of a university hospital. PATIENT(S): Uterine flushing was performed in 148 IVF patients. The first 100 patients were compared with a matched control group. INTERVENTION(S): Uterine flushing at the time of egg retrieval. MAIN OUTCOME MEASURE(S): IVP-ET results, pregnancy rates, and intrauterine LIF levels. RESULT(S): Pregnancy rates were not different in the group of patients with (27%) or without uterine flushing (28%). Leukemia inhibitory factor was detected in 60 patients (46%). Pregnancy rates did not differ between patients' detectable LIF and those in whom LIF was undetectable. Mean levels of LIF were 30.1 +/- 49.3 pg/mL and 28.6 +/- 51.2 pg/mL in pregnant and nonpregnant patients respectively. CONCLUSION(S): The flushing procedure at the time of egg retrieval did not adversely affect pregnancy rates. Leukemia inhibitory factor was detected in 46% of patients at the time of egg retrieval, but no correlation were observed with better pregnancy rates in patients with detectable LIF. Mean LIF levels did not differ in pregnant and nonpregnant women. Access to endoluminal secretions of the endometrium during IVF-ET may represent a new research in human implantation.     

Reducing the dose of human chorionic gonadotropin in high responders does not affect the outcomes of in vitro fertilization

OBJECTIVE: The lowest effective hCG dose in high responders during IVF-embryo transfer (ET) has not been established. This study was performed to confirm that a dose of 3,300 IU is sufficient to provide adequate oocyte maturation and fertilization. DESIGN: Retrospective review of IVF clinical data. SETTING: Infertility center at a tertiary care university. PATIENT(S): Ninety-four IVF cycles were analyzed from high responders based on peak E(2) levels. Demographics were compared including age, diagnosis, and stimulation protocol. INTERVENTION(S): On the day of hCG administration, if E(2) levels were >/=2,500 but <4,000 pg/mL, patients received 5,000 IU (group A). For levels between 4,000 pg/mL and 5,500 IU pg/mL, they received 3,300 IU (group B). MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, proportion of mature oocytes, fertilization rates, chemical and clinical pregnancy rates (PR). The incidence and severity of ovarian hyperstimulation syndrome (OHSS) was also analyzed. RESULT(S): Mean ages were 35.4 +/- 0.7 and 33.2 +/- 0.7 for groups A and B, respectively. Peak E(2) levels differed significantly (2,907 +/- 76 vs. 4,260 +/- 129 pg/mL), as well as the mean number of eggs retrieved (15.9 +/- 0.9 vs. 20.3 +/- 1.2). Proportion of mature eggs (81.6% vs. 81.9%), fertilization rate (70.5% vs. 68.7%), chemical PR (58.7% vs. 58.7%), and clinical PR (50.0% vs. 43.5%) were similar. There was no difference in the incidence of mild, moderate, or severe OHSS. CONCLUSION(S): A reduced hCG dose of 3,300 IU results in a similar proportion of mature eggs, similar fertilization rates, and similar PRs compared to 5,000 IU. Reducing the dose of hCG does not eliminate the risk of OHSS in a high-risk group.     

Morphologically poor blastocysts could affect the implantation rate of a morphologically good blastocyst during a double‐blastocyst transfer for patients who have experienced repeated implantation failures

Purpose

Increasing the number of transferred blastocysts sometimes is selected for patients with repeated implantation failure (RIF). To confirm this strategy, the pregnancy rates (PRs) were compared among the groups who had transferred either a single morphologically good blastocyst (MGB group), double blastocysts with both a MGB and a morphologically poor blastocyst (MGB + MPB group), or a double‐BT with 2 MGBs (two‐MGB group).

Methods

This study was performed between April, 2009 and September, 2014, including 634 cycles for 354 patients with RIF. All the patients received cryopreserved blastocysts in either hormone replacement or natural ovulatory cycles. The included MGBs were at more than the Gardner grade 3BB stage. The PR and implantation rates (IRs) among the three groups were statistically evaluated by the chi‐square test. Statistical significance was set at P < .01.

Results

Although the PRs were similar in these three groups, the IR in the MGB + MPB group was significantly lower than that of the MGB group. The rate in the two‐MGB group also was significantly lower than that of the MGB group.

Conclusion

A double‐BT with a MGB and a MPB does not increase the pregnancy rate, compared with a single‐BT with a MGB among patients with RIF.     

The influence of the depth of embryo transfer into the uterine cavity on implantation rate

ObjectiveTo assess the effect of the depth of embryo transfer replacement on implantation and clinical pregnancy rates in intracytoplasmic sperm injection cycles.Materials and methodsThis study was conducted on 90 consecutive patients. All patients underwent a standard down regulation protocol for ovarian stimulation. Oocytes retrieval was performed at 36h after HCG administration. Embryo transfer took place 2–4days after oocyte retrieval. The patients were grouped according to the distance between the tip of the catheter and the uterine fundus at transfer (group I <0.75cm, group II 0.75–<1.5cm, group III 1.5–2cm).ResultsImplantation and clinical pregnancy rates varied significantly between group I and other groups: 10.3% and 13.3%, respectively, in group I; 26.7% and 53.3%, respectively, in group II; 27.8% and 53.3%, respectively, in group III.ConclusionThe depth of embryo replacement inside the uterine cavity may influence implantation rates and should be considered as an important factor to improve the success of implantation and pregnancy rates.