Administration of prednisolone and low molecular weight heparin in patients with repeated implantation failures: a cohort study

Conflicting results exist for low molecular weight heparin (LMWH) and prednisolone when tested as separate adjuncts for the improvement of the clinical outcomes in patients with repeated implantation failures (RIF) undergoing IVF/ICSI treatment. Through a cohort study, we evaluated the combined effect of both drugs on pregnancy parameters in 115 women with RIF. Clinical pregnancy rate was the primary end point while the sample size was calculated through the results of a pilot study. Clinical and IVF cycle characteristics were also compared between the groups. Baseline and cycle characteristics were comparable between groups. Biochemical and clinical pregnancy rates were similar in both groups [23/57 (40.4%) vs. 14/58 (24.1%), and 17/57 (29.8%) vs. 11/58 (19%), p?=?.063, and .175, respectively]. Similarly, miscarriage rates were comparable between the groups (35.7% vs. 34.8%), as well as live birth rates [15/57 (26.3%) vs. 9/58 (15.5%), p?=?.154]. In conclusion, the administration of LMWH with prednizolone in subfertile women with RIF seems not to improve clinical pregnancy rates, but a full-scaled RCT would definitely be more accurate.     

Endometrial injury for RIF patients undergoing IVF/ICSI: a prospective nonrandomized controlled trial

To evaluate the effect of endometrial injury on clinical outcomes in subfertile women with repeated implantation failures (RIF) undergoing assisted reproduction. In this prospective nonrandomized controlled trial, 103 subfertile women with RIF were included. Fifty-one underwent endometrial injury through hysteroscopy in the early follicular phase of the previous cycle and 52 underwent the standard protocol without any intervention. Live birth and miscarriage were the primary outcomes. Clinical and in vitro fertilization (IVF) cycle characteristics, were also compared between groups. Both groups were comparable in terms of baseline and cycle characteristics. Live birth rates were significantly higher in the study, compared with the control group (18/51 vs. 8/52, odds ratio (OR)?=?0.25; 95% confidence interval (CI)?=?0.10–0.64; p?=?0.020), although miscarriage rates were similar (7/51 vs. 10/52, OR=?0.25; 95%CI=?0.12–0.66; p?=?0.452). The rest of the outcomes parameters were comparable between groups. Logistic regression analysis revealed that endometrial injury and duration of subfertility were independent predictors of live birth after control of other variables (OR?=?2.818; 95%CI?=?1.044–7.605; p?=?0.041 and OR?=?0.674; 95%CI?=?0.461–0.985, p?=?0.042, respectively). Endometrial injury induced through office hysteroscopy in the preceding cycle in subfertile women with RIF improves live birth rates.     

Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin

OBJECTIVE: To evaluate the use of low-molecular-weight heparin (LMWH) in combination with low-dose aspirin (LDA) for the treatment of antiphospholipid antibody (APA)-associated recurrent pregnancy loss and to compare the results with the use of unfractionated heparin (UFH) plus LDA. DESIGN: Prospective, controlled, multicenter pilot study. SETTING: Two academically based reproductive health centers. PATIENT(S): Patients with three or more pregnancy losses and positive APA. INTERVENTION(S): Patients were treated with LMWH and LDA (n = 25) or UFH and LDA (n = 25). MAIN OUTCOME MEASURE(S): Fetal outcome and maternal complications from treatments were compared between the two treatment groups. RESULT(S): Of the 25 patients in the LMWH group, 21 (84%) delivered a viable infant and 4 (16%) miscarried. Of the 25 patients in the UFH group, 20 (80%) delivered a viable infant and 5 (20%) miscarried. These differences were not statistically significant. No major bleeding episodes occurred during pregnancy or at the time of delivery. No cases of deep venous thrombosis, thrombocytopenia, pre-eclampsia, gestational diabetes, or bone fractures were noted in either of the two groups. CONCLUSION(S): In this pilot study, the use of LDA in combination with LMWH during pregnancy for the prevention of recurrent pregnancy loss in women with antiphospholipid syndrome seems to be as safe as UFH plus LDA. Large, randomized trials will be required to determine differences in outcome with LMWH and LDA compared with treatment with UFH combined with LDA in this group of patients.     

The role of low-molecular-weight heparin in recurrent implantation failure: a prospective, quasi-randomized, controlled study

Low-molecular-weight heparin did not provide any beneficial effect on pregnancy outcomes in patients with two or more implantation failures. Further trials are needed to confirm a trend in favor of low-molecular-weight heparin in the subgroup with women with three or more implantation failures.     

Recurrence and severity of abnormal pregnancy outcome in patients treated by low-molecular-weight heparin: a prospective pilot study

Objective: This prospective pilot study assesses the recurrence rate and severity of abnormal pregnancy outcome (APO), excluding early pregnancy complications, in pregnant patients, without acquired thrombophilia, treated by prophylactic doses of low-molecular-weight heparin (LMWH), independently from their congenital thrombophilic condition. Methods: We recruited a cohort of 128 pregnant patients with previous APO; 100 of whom with APO and intrauterine growth restriction (IUGR) and 28 with maternal APO only. LMWH treatment was started at recruitment. Composite cross-over recurrence rate IUGR, gestational hypertension, preeclampsia, help syndrome, abruptio placenta were analyzed. The main outcome measure was severe APOs with iatrogenic delivery ≤ 32 weeks of gestation. Results: Median gestational age at LMWH treatment was 20 weeks. Severe APO decreased in treated pregnancies from 45% to 4% (relative risk = 0.3, confidence interval 95% = 0.2–0.8). This value was not significantly different in thrombophilic and nonthrombophilic patients. When severe and minor complications were analyzed altogether, the recurrence rate was 28%. In patients with APO and fetal growth restriction (FGR) in the index pregnancy, newborn weights were significantly better in the treated pregnancy: 1090 g (1035–1145) vs. 850 g (535–1200), p < 0.01. Conclusions: Prophylactic regimen of LMWH significantly reduced the recurrence rate of severe composite APO in pregnancies affected in the index pregnancy by APO and FGR or small for gestational age newborns. This result was independent from the patients’ inherited thrombophilic conditions.     

Corifollitropin alfa compared with follitropin beta in GnRH-antagonist ovarian stimulation protocols in an unselected population undergoing IVF/ICSI

Recombinant DNA technologies have produced Corifollitropin alfa (CFa) used during IVF/ICSI in order to keep the circulating FSH levels above the threshold necessary to support multi-follicular growth for a week. In this prospective case-control study, we compared 70 participants treated with 150?μg CFa combined with 150?IU of follitropin beta (study group) with 70 subfertile participants with matching baseline characteristics, conforming with the same inclusion criteria and treated with an antagonist protocol using follitropin beta (control group). Live birth was the primary outcome, while secondary outcome measures were IVF/ICSI cycles characteristics, including adverse events and complications. Live birth was determined in reduced rates in the study compared to the control group, reaching statistical significance [6/70 versus 20/70, p?=?0.002], as also in the respective number of clinical pregnancies [9/70 versus 23/70, p?=?0.005], although the incidence of miscarriage was similar for both groups [6/70 versus 5/70, p?>?0.99]. Most of the secondary parameters examined were similar between groups. Logistic regression revealed that protocol and AFC had a direct impact on live birth. Ovarian stimulation with CFa does not seem to constitute an equally effective method as compared with follitropin beta to be offered in a general subfertile population seeking IVF/ICSI treatments.     

Birthweight in pregnant women with protein S deficiency treated with low-molecular-weight heparin: a retrospective cohort study

Objective: To determine the risk of small-for-gestational-age (SGA) and intrauterine growth retardation (IUGR) in pregnant women with protein S (PS) deficiency who received low-molecular-weight heparin (LMWH).

Methods: Retrospective cohort study of pregnant women seen from January 2002 to December 2011. The study cohort comprised a total of 328 patients with PS deficiency, who received prophylactic enoxaparin during pregnancy. The control cohort included 11 884 pregnant women without significant past medical history. The risk of SGA and IUGR was calculated as odds ratio. Multivariate regression analysis over the entire reference population was performed determining the risk of both SGA and IUGR by adjusting for maternal age, first delivery, maternal underweight status, pre-eclampsia, other treated thrombophilias or history of recurrent abortion.

Results: The SGA rates in the PS deficiency and control cohorts were 10.7% and 8.5%, respectively (p?>?0.05). There was no increased risk of SGA (unadjusted OR?=?1.28, 95% confidence interval [CI] 0.9–1.83; adjusted OR?=?1.35, 95% CI 0.91–2.01). The IUGR rate was 2.7% in pregnant women with PS deficiency versus 4.1% in the control group (p?>?0.05). Also, we did not find a significant risk of IUGR (OR?=?0.66; 95% CI 0.34–1.28; adjusted OR?=?0.843; 95% CI 0.42–1.70).

Conclusions: In women with PS deficiency treated with LMWH, the risk of SGA and IUGR is similar to the one found in healthy pregnant women.     

104例常规IVF低受精率周期行补救ICSI临床结局分析

目的评估常规IVF低受精率周期行补救ICSI（rescue intracytoplasmic sperm injection,R-ICSI）的临床结局。方法回顾分析了本中心2009年1月至2012年6月,104例常规IVF低受精率周期行R-ICSI的结果。结果 104例周期中,常规IVF的2PN数只有1个是85例,最后2PN没有形成可利用胚胎是18个周期;常规IVF的2PN数大于等于2个有19例,最后2PN没有形成可利用胚胎是1个周期。结论 2PN数是1个常规IVF低受精率周期,为了避免移植周期取消,可以行R-ICSI。2PN数大于等于2个的周期,根据未受精MⅡ卵数决定是否行R-ICSI。     

Safety of low-molecular-weight heparin during pregnancy: a retrospective controlled cohort study

Objective

To study the safety of low-molecular-weight heparin (LMWH) treatment during pregnancy for the mother and the foetus.

Study design

Retrospective controlled cohort study. Six hundred and forty-eight pregnancies exposed to LMWH were compared with 626 unexposed pregnancies. Principal characteristics, indications for LMWH use, and maternal and foetal complications were reported for each pregnancy. Data were obtained from patients’ electronic hospital records and analysed using Statistical Package for the Social Sciences Version 17.0.

Results

The incidence rates of various pregnancy complications did not differ between the groups (LMWH group vs control group): 1.56% vs 1.1% for thrombocytopenia, 8.7% vs 6.5% for preterm delivery, 0.7% vs 0.3% for stillbirth, 1.4% vs 1.0% for severe pre-eclampsia, 2.7% vs 2.2% for foetal growth restriction, and 10.7% vs 7.8% for antenatal bleeding. One serious antenatal maternal haemorrhage occurred in the LMWH group (0.15%), but this was unrelated to LMWH use. The caesarean section rate and the amount of bleeding during delivery were similar in the two groups (21% vs 19% and 500 vs 450 ml, respectively). The risk of major blood loss during labour (>1000 ml) was no higher in the LMWH group compared with the control group. The incidence of allergic skin reactions was 0.3% in the LMWH group. No heparin-induced thrombocytopenia or symptomatic osteoporotic fractures were observed. Recurrent venous thromboembolic events occurred in 2.5% of patients in the LMWH group.

Conclusion

This study indicates that the use of LMWH is safe during pregnancy.     

Morphokinetic parameters of early embryo development via time lapse monitoring and their effect on embryo selection and ICSI outcomes: a prospective cohort study

Purpose

To compare the outcomes of embryos selected via time lapse monitoring (TLM) versus those selected with conventional methods of selection in subfertile women undergoing ICSI.

Methods

The study population (239 women) was classified into two groups, based on the monitoring method used: Group 1 (TLM) and Group 2 (conventional monitoring). Groups were compared according to the clinical and ICSI cycle characteristics and reproductive outcomes, while transfers were performed at day 2 or 3. Subgroup analyses were performed, in women of both groups according to age and clinical parameters, and in embryos of Group 1 based on their cellular events.

Results

There was a statistically significant difference between the two study groups with regard to the outcome parameters, favoring Group 1 and especially in women >40 years of age. No differences were found in subgroup analyses in participants of both groups, regarding the stimulation protocol used, number of the oocytes retrieved and type of subfertility, while in Group 1 the percentages of “in range” cellular events were higher in certain divisions in ages 35–40, non-smokers, and the GnRH-agonist group, and in embryos that resulted in pregnancy.

Conclusion

Morphokinetic parameters of early embryo development via TLM are related to the characteristics of subfertile patients and associated with ICSI outcomes.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0436-z) contains supplementary material, which is available to authorized users.     

Pregnancy and miscarriage rates in 3978 donor insemination cycles: Effect of age,parity and partner's infertility status on pregnancy outcome

The effects of age, parity and male infertility status on pregnancy outcome were studied in a cohort of 720 women receiving donor insemination (DI) treatment. Twenty-two percent of women failed to complete the treatment, leaving 562 women receiving 3202 cycles of DI for assessment. Of the 321 of pregnancies achieved, 57 (17.8%) ended in a mis-carriage. After further DI treatments, 64.7% of mothers who had miscarried succeeded in giving birth. There was some evidence to indicate a trend of decreasing pregnancy rate with increasing maternal age, although this result was not significant (log rank trend statistics = 3.44, P > 0.05). The pregnancy rates of multiparous and primiparous women were significantly different, irrespective of their partner's infertility status (azoospermia: log rank statistics = 3.74, P ˇ- 0.05; oligozoospermia: log rank statistics = 4.71, P < 0.03). Furthermore, multiparous women were more likely to become pregnant than primiparous women (azoospermia: hazard ratio = 1.29; oligozoospermia: hazard ratio = 1.50). There was no significant association between miscarriage rate and maternal age (log rank trend statistics = 0.99, P > 0.05). The small number of older women (> 35 years) may confound this result. The mean (± sd) sperm donor age was 23.6 years (± 3.5 years). The implications of these observations are discussed.     

Low-molecular-weight heparin and aspirin use in relation to pregnancy outcome in women with systemic lupus erythematosus and antiphospholipid syndrome: A cohort study

Objective: To relate anticoagulant use to pregnancy complications in women with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). Methods: All ongoing pregnancies, 184, in two Dutch tertiary centers between 2000 and 2015. Results: LMWH and aspirin was prescribed in 15/109 SLE women without antiphospholipid antibodies (aPL), 5/14 with aPL, 11/13 with APS, 45/48 with primary APS. Main complications in the four treatment groups (no anticoagulant treatment, aspirin, LMWH, aspirin and LMWH) included hypertensive disorders of pregnancy (9.4%, 23.3%, 50%, 18.4%, respectively, p = 0.12) and preterm birth (16.7%, 34.3%, 75%, 36.8%, respectively, p < 0.001). Conclusion: Maternal and perinatal complications occurred frequently, despite LMWH and aspirin use.     

Intracytoplasmic morphologically selected sperm injection (IMSI) after repeated IVF or ICSI failures: a prospective comparative study

Objective

Sperm morphology plays a significant role in assisted reproductive technologies and is associated with high implantation rates. The objective of this study was to evaluate the outcome of intracytoplasmic morphologically selected sperm injection (IMSI) after repeated failures of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) techniques.

Study design

In a prospective study in which couples acted as their own controls, 75 infertile couples were offered IMSI after at least two previous IVF or ICSI failures. The main outcome measures were embryo quality and number of blastocysts obtained.

Results

The percentage of top quality embryos obtained at day 2 was increased in IMSI compared to IVF/ICSI cycles (89.8% versus 79.8%; p = 0.009). Extended embryo culture was possible in 41.3% of IMSI cycles versus 26.7% of IVF/ICSI cycles (p = 0.04), and the mean number of blastocysts obtained was higher in IMSI cycles (1.5 ± 1.9) than in IVF/ICSI cycles (1.0 ± 1.2) (p = 0.03). Moreover, IMSI resulted in clinical pregnancy and birth rates of respectively 29.3% and 18.6%.

Conclusion

After two or three IVF/ICSI failures, IMSI seems to give better embryo quality and more blastocysts, which allow more embryo transfers at the blastocyst stage. This study supports the use of sperm ultramorphology examination as an independent test to be proposed after repeated IVF or ICSI failures.     

Oral oestradiol supplementation as luteal support in IVF/ICSI cycles: a prospective,randomized controlled study

Objective

To explore whether oral oestradiol (E2) supplementation (6 mg) in the luteal phase is beneficial to the outcome of patients undergoing gonadotrophin-releasing hormone agonist (GnRHa) long protocol in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles.

Study design

Prospective, randomized, controlled study at the IVF Clinic, Sun Yat-sen Memorial Hospital. In total, 402 patients with an indication for IVF or ICSI were recruited. Patients were prospectively randomized to receive either progesterone injection plus oral E2 supplementation (Group A, n = 202) or progesterone injection alone (Group B, n = 200) as luteal support after oocyte retrieval. The main outcome measure was the clinical pregnancy rate.

Results

No significant difference in the clinical pregnancy rate or miscarriage rate was observed between Group A and Group B (50.9% vs 58.0%, 14.6% vs 11.2%; p > 0.05). In different age subgroups (≤35 years and >35 years) all measurements were comparable in patients with or without E2 supplementation, as well as in subgroups with different E2 levels on the day of human chorionic gonadotrophin injection (E2 ≥ 3000 pg/ml and E2 < 3000 pg/ml).

Conclusion

Adding E2 as luteal support did not increase the clinical pregnancy rate or reduce the miscarriage rate. Routine use of a combination of E2 and progesterone as luteal support in GnRHa long protocol IVF/ICSI cycles is not recommended.     

Prognostic factors for patients undergoing vitrified-warmed human embryo transfer cycles: a retrospective cohort study

We examined the prognostic factors for pregnancy in 210 vitrified-warmed embryo transfer (ET) cycles in 121 patients. The univariate analysis showed that age, gravida, the number of cycles associated with infertility caused by endometriosis, the number of previous assisted reproductive technology (ART) treatment cycles, and the number of ICSI procedures were significantly lower in pregnant cycles compared with non-pregnant cycles. The percentages of ET using at least one intact embryo and of ET using at least one embryo that had developed further after warming were significantly higher in pregnant cycles compared with non-pregnant cycles. Multivariate logistic regression analysis showed that previous ART treatment cycles, ET with at least one intact embryo, and ET using at least one embryo that had developed further were independent prognostic factors for pregnancy in vitrified-warmed ET cycles. We conclude that fewer previous ART treatment cycles, ET using at least one intact embryo, and ET with embryos that have developed further after warming might be favourable prognostic factors for pregnancy in vitrified-warmed ET cycles.     

The impact of unicornuate uterus on perinatal outcomes after IVF/ICSI cycles: a matched retrospective cohort study

Objective: To evaluate the impact of unicornuate uterus on perinatal outcomes after in vitro fertilization and/or intracytoplasmic sperm injection (IVF/ICSI) cycles.

Methods: We performed a retrospective cohort study including 160 women with unicornuate uterus and 1:1 matched controls with normally shaped uterus. They received IVF/ICSI treatment during January 2009 and December 2011. The perinatal outcomes were followed up till December 2014.

Results: There were no significant differences in pregnancy rate, clinical pregnancy rate or live birth rate (53.6 versus 52.7, 41.4 versus 43.5, 33.8% versus 31.8%) between unicornuate uterus group and controls. Their biochemical pregnancy rate (22.8 versus 17.5%) and miscarriage rate (16.0 versus 18.8%) were similar. No significant differences were identified in preterm birth rate (18.3 versus 11.8%), birthweight (3.24?±?0.60 versus 3.33?±?0.54?kg) or birth length (50.47?±?2.33 versus 50.06?±?2.40?cm) among the singletons. However, lower gestational age (35.56?±?2.68 versus 36.71?±?1.73, p?=?.019), higher preterm birth rate (55.0 versus 34.4%, p?=?.038), lower birthweight (2.33?±?0.58 versus 2.69?±?0.38?kg, p?=?.001), lower birth length (45.33?±?2.46 versus 48.88?±?2.06?cm, p?=?.000), as well as higher rate of very low birthweight (13.2% versus 0, p?=?.007) were found for the twins from unicornuate uterus group.

Conclusions: The results indicated unimpaired pregnancy and perinatal outcomes for women with unicornuate uterus conceiving one fetus. However, close attention should be paid to twin pregnancy in unicornuate uterus owing to increased risks of prematurity and low birthweight. Selected single embryo transfer is recommended for women with unicornuate uterus undergoing IVF/ICSI cycles.     

体外受精D2/D3胚胎移植与异位妊娠关系探讨

目的:探讨体外受精第2天(D2)或第3天(D3)移植的异位妊娠发生率有无统计学差异。方法:回顾性分析2009年3月至12月郑州大学第一附属医院生殖中心接受IVF-ET助孕的754周期、ICSI助孕的599周期的临床资料。结果:IVF-ET:<35岁的D2组和D3组异位妊娠率分别为0.00%、5.63%,≥35岁的D2组和D3组异位妊娠率分别为4.35%、4.76%;ICSI:<35岁的D2组和D3组异位妊娠率分别为4.17%、4.05%,≥35岁的D2组和D3组异位妊娠率分别为7.14%、7.69%,均无显著统计学差异(P>0.05)。结论:体外受精D2/D3移植异位妊娠率无显著统计学差异,可根据患者具体临床情况来决定移植时间。     

Outcomes of 1503 cycles of modified natural cycle in vitro fertilization: a single-institution experience

PurposeA retrospective cohort study was conducted in a single academic center to determine if modified natural cycle in vitro fertilization (mnIVF) is an acceptable treatment for the infertile couple.MethodsCycles performed between July 2005 and December 2011 were included. In our center’s mnIVF protocol, a GnRH antagonist, gonadotrophin, as well as Indocid are given on a daily basis from detection of a dominant follicle until ovulation induction. The primary outcomes were clinical pregnancy rates (CPR) per cycle started and per embryo transfer (ET). Outcomes were stratified by female patient age (≤35 years and ≥36 years). They were further stratified in each age group by ovarian response status according to the 2011 Bologna criteria.ResultsA total of 1503 cycles of mnIVF, performed in 782 patients, were analyzed. CPRs were 13.7 % per started cycle and 32.5 % per ET. Stratification by ovarian response status (normal or poor) in each age group showed similar CPRs in patients ≤35 years (p = 0.373), and divergent CPRs per ET in patients ≥36 years old (26.26 vs 6.25 %).ConclusionMnIVF is an acceptable treatment option for patients considering IVF, particularly for women ≤35 years old and for women ≥36 years old with normal ovarian response.     

Embryological indicators in cycles with HCG or different doses of GnRH-a for the final oocyte maturation in IVF–ICSI patients

Abstract

So far there is no consensus on the optimal dosage of GnRH-a when using it as a trigger for final oocyte maturation in in vitro fertilization (IVF) cycles. We compared embryological characteristics in IVF–intra-cytoplasmic sperm injection (ICSI) cycles when applying triptorelin at a dose of 0.2?mg (test group 2), 0.5?mg (test group 3) and human chorionic gonadotropin (HCG) at a dose of 10?000?IU (test group 1). In group 1, the average number of oocytes per oocyte retrieval (11.7?±?4.8) was lower in comparison with groups 2 and 3, which can be explained by the differences in the selection of the patients’. The number of oocytes per retrieval in group 3 (20.2?±?6.3) was significantly higher (p?=?0.02) compared to group 2 (17.0?±?6.2). The percentage of mature oocytes (MII) and fertilization rate did not differ between the groups. The rate of blastocyst formation in group 3 (71.9?±?17.1%) was significantly higher (p?=?0.02) in comparison with group 2 (57.9?±?24%). We conclude that the application of triptorelin at a dose of 0.5?mg may be more effective for triggering final oocyte maturation in IVF cycles in comparison with the dose of 0.2?mg, due to the increase in the number of retrieved oocytes and the improved rate of the blastocyst formation.