IVF Failure Research Articles

Hysteroscopy Findings in Failed IVF and their Influence on Pregnancy Outcome

Hysteroscopy Findings in Failed IVF and their Influence on Pregnancy Outcome

Day-2 and day-3 sequential transfer improves pregnancy rate in patients with repeated IVF–embryo transfer failure: a retrospective case–control study

The purpose of this study was to evaluate the effect of sequential embryo transfer in patients with repeated IVF failure. A retrospective matched case–control study was conducted and the outcomes of 213 patients with a history of repeated IVF–embryo transfer failure were analysed, of which 33 women underwent sequential embryo transfer on day 2 and day 3 (D2/D3 group), 66 women on day 3 and day 5 (D3/D5 group), 85 women underwent day-3 embryo transfer only (D3 control group) and 29 women underwent day-5 embryo transfer only (D5 control group) in the assisted reproduction centre of the Sixth Affiliated Hospital of Sun Yat-sen University from August 2010 to December 2011. The results showed that the clinical pregnancy rate of the D2/D3 group was higher than that of the D3 group (48.5% versus 22.4%, P=0.006) while the clinical pregnancy rates of the D3/D5 and D5 groups were not significantly different (50.9% versus 45.8%). Day-2 and day-3 sequential embryo transfer may improve the clinical outcomes for patients with repeated IVF–embryo transfer failures.The purpose of this study was to evaluate the effect of sequential embryo transfer in patients with repeated IVF failure. A retrospective matched case–control study was conducted and the outcomes of 213 patients with a history of repeated IVF–embryo transfer failure were analysed, of which 33 women underwent sequential embryo transfer on day 2 and day 3 (D2/D3 group), 66 women on day 3 and day 5 (D3/D5 group), 85 women underwent day-3 embryo transfer only (D3 control group) and 29 women underwent day-5 embryo transfer only (D5 control group) in the assisted reproduction centre of the Sixth Affiliated Hospital of Sun Yat-sen University from August 2010 to December 2011. The results showed that the clinical pregnancy rate of the D2/D3 group was higher than that of the D3 group (48.5% versus 22.4%, P=0.006) while the clinical pregnancy rates of the D3/D5 and D5 groups were not significantly different (50.9% versus 45.8%). Day-2 and day-3 sequential embryo transfer may improve the clinical outcomes for patients with repeated IVF–embryo transfer failures.

Hysteroscopic Outpatient Metroplasty To Expand Dysmorphic Uteri (HOME-DU Technique)

In this video we describe a novel minimally invasive technique intended at obtaining an increase of the volume of uterine cavity of dysmorphic uteri (i.e. uterine hypoplasia, T-shaped uterus, tubular-shaped uterus) in women with reproductive failure (early spontaneous miscarriage or IVF failure). This technique, named HOME-DU (Hysteroscopic Outpatient Metroplasty to Expand Dysmorphic Uteri), is performed in the outpatient setting under conscious sedation using an office continuous flow operative hysteroscope and a 5Fr bipolar electrode.

C0360 Clinical value of thrombophilia diagnostics in women with repeated IVF failure

C0360 Clinical value of thrombophilia diagnostics in women with repeated IVF failure

THE MANAGEMENT OF WOMEN WITH THROMBOPHILIA IN PREPARATION FOR IN VITRO FERTILIZATION

The aim was to study changes in the hemostatic system in women with hereditary and acquired thrombophilia in IVF cycle, the possibility of their drugs correction, as well as the effect of this therapy on the outcome of IVF. We examined 119 women with congenital or acquired thrombophilia during preparation or during IVF cycle. In the presence of abnormalities in laboratory data, combination of weight adjusted dose of the low molecular weight heparin, low dose aspirin and folic acid administered to the severity of coagulation disorders and homocystein level. In the group of patients with a history 3 or more IVF failures APS was diagnosed in 36.6 % of women. In this group the frequency of mutations in genes: PAI-1, PLAT, fibrinogen was significantly higher than in control group (83.3 % and 58.33 %, 40 % and 19.44 %, 50 % and 25 % respectively, p < 0.05), as well as mutations in genes PAI-1 and PLAT combination rate (31.03 % and 13.89 % respectively, p < 0,05) and the frequency of combinations of 3 or more mutations (65.51 % and 19.44 %, p < 0.001). In the group of women with thrombophilia (n = 97) treated with this therapy 52.57 % IVF cycles was successful. At 36.08 % pregnancies ended with childbirth. In the subgroup of women with 3 or more IVF failures (n = 26) the pregnancy rate was 38.46 %.

Rates of major depression following IVF failure

Rates of major depression following IVF failure

The effect of transvaginal endometrial perfusion with granulocyte colony-stimulating factor (G-CSF)

The effect of transvaginal endometrial perfusion with granulocyte colony-stimulating factor (G-CSF)

Are the annexin V microbeads, a real solution to sperm DNA fragmentation?

ObjectiveThe aim of our study was to assess the effect of annexin V microbeads on cycles with abnormal sperm DNA fragmentation (>20%), in fertilization, embryo quality and success rate.DesignAnalytic Retrospective Observational study.Materials and MethodsWe analyzed 88 cycles of Assisted Reproduction treatments.All patients had abnormal sperm DNA fragmentation and previously had undergone one or more unsuccessful cycles of IVF/ICSI.The cycles were divided into two groups:Group 1: unsuccessful cycles of IVF/ICSI.Group 2: cycles with sperm sorting with annexin V columns (36 cycles) from these same partners.The sperm DNA fragmentation was assessed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling).The embryos were evaluated according to criteria of the Spanish Association for Reproductive Biology (ASEBIR). The transfer was performed on day 3 of embryo development.ResultsNo significant differences were found between groups or age, nor in the rates of fertilization (P>0.05). However, embryo quality did show statistically significant differences, being higher the number of top quality embryos (A, P=0.004. A+B, P=0.02) in group 2.ConclusionThe results suggest that the use of annexin V columns improves embryo quality in couples with previous failure in IVF/ICSI. So it could be used, as a useful tool, in patients with previous IVF failures. The fertilization rate shows no significant differences. This may be because sperm with fragmented DNA were capable of fertilizing the egg as effectively as sperm without DNA fragmentation. ObjectiveThe aim of our study was to assess the effect of annexin V microbeads on cycles with abnormal sperm DNA fragmentation (>20%), in fertilization, embryo quality and success rate. The aim of our study was to assess the effect of annexin V microbeads on cycles with abnormal sperm DNA fragmentation (>20%), in fertilization, embryo quality and success rate. DesignAnalytic Retrospective Observational study. Analytic Retrospective Observational study. Materials and MethodsWe analyzed 88 cycles of Assisted Reproduction treatments.All patients had abnormal sperm DNA fragmentation and previously had undergone one or more unsuccessful cycles of IVF/ICSI.The cycles were divided into two groups:Group 1: unsuccessful cycles of IVF/ICSI.Group 2: cycles with sperm sorting with annexin V columns (36 cycles) from these same partners.The sperm DNA fragmentation was assessed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling).The embryos were evaluated according to criteria of the Spanish Association for Reproductive Biology (ASEBIR). The transfer was performed on day 3 of embryo development. We analyzed 88 cycles of Assisted Reproduction treatments.All patients had abnormal sperm DNA fragmentation and previously had undergone one or more unsuccessful cycles of IVF/ICSI.The cycles were divided into two groups: Group 1: unsuccessful cycles of IVF/ICSI. Group 2: cycles with sperm sorting with annexin V columns (36 cycles) from these same partners. The sperm DNA fragmentation was assessed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling).The embryos were evaluated according to criteria of the Spanish Association for Reproductive Biology (ASEBIR). The transfer was performed on day 3 of embryo development. ResultsNo significant differences were found between groups or age, nor in the rates of fertilization (P>0.05). However, embryo quality did show statistically significant differences, being higher the number of top quality embryos (A, P=0.004. A+B, P=0.02) in group 2. No significant differences were found between groups or age, nor in the rates of fertilization (P>0.05). However, embryo quality did show statistically significant differences, being higher the number of top quality embryos (A, P=0.004. A+B, P=0.02) in group 2. ConclusionThe results suggest that the use of annexin V columns improves embryo quality in couples with previous failure in IVF/ICSI. So it could be used, as a useful tool, in patients with previous IVF failures. The fertilization rate shows no significant differences. This may be because sperm with fragmented DNA were capable of fertilizing the egg as effectively as sperm without DNA fragmentation. The results suggest that the use of annexin V columns improves embryo quality in couples with previous failure in IVF/ICSI. So it could be used, as a useful tool, in patients with previous IVF failures. The fertilization rate shows no significant differences. This may be because sperm with fragmented DNA were capable of fertilizing the egg as effectively as sperm without DNA fragmentation.

NLF2 gene expression in the endometrium of patients with implantation failure after IVF treatment

The aim of this study was to analyze the expression of microfibril-associated protein 2 (MFAP2), microfibril-associated protein 5 (MFAP5) and nuclear localized factor 2 (NLF2) genes in patients with repeated IVF failure and compare with fertile population. Total RNA was isolated from 38 patients (repeated implantation failure, group 1, n=22; fertile patients, group 2, n=16). mRNA expression levels were measured quantitatively using real-time polymerase chain reaction. Our results showed that mRNA expression of NLF2 significantly decreased in the infertility group as compared to control group (P=0.023). In addition a marked decrease was observed in the expression of MFAP2 in women with repeated implantation failure. In conclusion, NLF2 gene expression levels and differences in MFAP2 and MFAP5 gene expressions (albeit being insignificant) between infertile group and control group draw attention to a genetic basis under implantation failure.

Previous abortion is a positive predictor for ongoing pregnancy in the next cycle in women with repeated IVF failures

Early pregnancy loss is common among women treated with assisted reproduction treatment, but whether it is a prognostic factor for success in subsequent IVF cycles is not well established. The aim of this study was to determine whether a biochemical pregnancy (BP) or spontaneous abortion (SA) affects the pregnancy rates in the following cycle. A retrospective study of 2687 women undergoing 6678 cycles between January 1998 and March 2010 was performed. Ongoing pregnancy rate (PR) per cycle was compared between patients with a pregnancy loss versus a negative β-HCG in their previous cycles. Multivariate analysis of factors affecting ongoing pregnancy rate was performed. BP and/or SA in the first three cycles did not significantly alter the chances to conceive (16.9% patients with BP and/or SA in the previous cycle versus 16.5% patients with no previous pregnancy). From cycle 4 onwards, the presence of a previous abortion (either BP or SA) was associated with better ongoing PR (23.0% versus 11.2%, P<0.001). In conclusion, BP and/or SA in a previous cycle appears to be a positive marker for success in subsequent cycles in patients with repeated IVF failures. These results should be further investigated in this challenging group of patients.Pregnancy loss in the first trimester is common among women treated with assisted reproduction treatment, but its significance regarding chances of future ongoing pregnancies is not well established. The aim of this study was to determine whether an early pregnancy loss during an IVF cycle, affects the ongoing pregnancy rates in following IVF cycles. A retrospective study of 2687 women undergoing 6678 IVF cycles between January 1998 and March 2010 was performed. Ongoing pregnancy rate was compared between patients with a pregnancy loss in their previous IVF cycle versus patients who failed to conceive (negative-human chorionic gonadotrophin blood test) in their previous IVF cycle. A multivariate analysis of factors affecting ongoing pregnancy rate including age, number of embryos transferred and aetiology of infertility was performed. We found that early pregnancy loss during the first three IVF cycles did not significantly alter the chances to conceive (pregnancy rates: 16.9% for patients with early pregnancy loss in the previous cycle compared to 16.5% in patients who didn’t conceive in the previous cycle). From cycle 4 onwards, the presence of a previous early pregnancy loss was associated with better ongoing pregnancy rate (23.0% compared to 11.2%, P<0.001). In conclusion, early pregnancy loss in the previous cycle appears to be a positive marker for success in subsequent cycles in patients with repeated IVF failures.

Psychological distress and in vitro fertilization outcome

To examine whether psychological distress predicts IVF treatment outcome as well as whether IVF treatment outcome predicts subsequent psychological distress. Prospective cohort study over an 18-month period. Five community and academic fertility practices. Two hundred two women who initiated their first IVF cycle. Women completed interviews and questionnaires at baseline and at 4, 10, and 18 months' follow-up. IVF cycle outcome and psychological distress. In a binary logistic model including covariates (woman's age, ethnicity, income, education, parity, duration of infertility, and time interval), pretreatment depression and anxiety were not significant predictors of the outcome of the first IVF cycle. In linear regression models including covariates (woman's age, income, education, parity, duration of infertility, assessment point, time since last treatment cycle, and pre-IVF depression or anxiety), experiencing failed IVF was associated with higher post-IVF depression and anxiety. IVF failure predicts subsequent psychological distress, but pre-IVF psychological distress does not predict IVF failure. Instead of focusing efforts on psychological interventions specifically aimed at improving the chance of pregnancy, these findings suggest that attention be paid to helping patients prepare for and cope with treatment and treatment failure.

Detailed analysis of peripheral blood natural killer cells in women with repeated IVF failure

Detailed analysis of peripheral blood natural killer cells in women with repeated IVF failure

G-CSF treatment improves IVF outcome in women with recurrent implantation failure in IVF

Does the administration of intravenous intralipid in women with previous implantation failure at the time of embryo transfer improve pregnancy outcomes in terms of biochemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and ongoing pregnancy rate?This was a single blinded randomised controlled trial of 105 subjects with previous failed IVF undergoing self donor oocyte IVF/ICSI from January 2017 to May 2018. Randomisation was by computer generated sequence after oocyte pickup. Results were analysed for 102 women, excluding three women due to poor embryo quality. Women in the study arm(n = 52) received 2 doses of 20% intravenous intralipid (Fresenius Kabi), 4 ml diluted in 250 ml normal saline by slow infusion. The first dose was given immediately after oocyte recovery, and the second dose was given on the day of embryo transfer, 1 h prior to the transfer. The control group (n = 50) received normal saline. Flexible ovarian stimulation protocols were used. All the women received routine luteal phase support with micronised vaginal progesterone.102 women underwent analysis, 52 in the study group and 50 in control group. There was no significant difference in the baseline characteristics. There was a significant difference in the biochemical pregnancy rate in the intralipid group (40.38%) versus control (16%) [(p = 0.006), RR = 2.5 (1.23–5.16 CI)], clinical pregnancy rate [(34.62% vs 14%), p = 0.006, RR = 2.5(1.13–5.40 CI)], implantation rate [(16.6% vs 6.6%), p = 0.012, RR = 2.5(1.18 to 5.41 CI)], and take home baby rate [28.8% vs 10%, p = 0.024, RR = 2.8(1.1–7.3)]. The adjusted odds ratio for clinical pregnancy in women who received intralipid vs placebo was 3.1 (1.02–9.70 95% CI), p = 0.046. No adverse effects of intralipid were observed.This study shows a statistically significant increase in implantation rate and live birth rate in women who receive intravenous intralipid with prior implantation failure after IVF/ICSI. These findings concur with other studies; however, literature is limited. The effect of intralipid on the immunological abnormalities in women who experience recurrent implantation failure needs to be investigated further.

Influence of zona pellucida thickness on fertilization, embryo implantation and birth

Defective sperm–zona pellucida binding and penetration are the main causes of IVF failure. The purpose of this study was to evaluate the effect of zona pellucida thickness in fertilization failure and test the influence of zona pellucida thickness on implantation and birth in rabbits. Embryos and oocytes were collected from 72 females on Day 2 post-insemination. A total of 559 normal embryos were recovered; 402 embryos were transferred by laparoscopy and 157 embryos were used to measure the zona pellucida thickness using the ImageJ program. Laparoscopies were also performed on all does at Day 12 of gestation to record the number of implanted embryos. Litter size at birth was recorded. The mean zona pellucida thickness of the 157 embryos and of the 64 control group oocytes (18.3±0.2 and 18.5±0.3μm, respectively) was significantly less than the zona pellucida thickness of the 74 failed fertilization oocytes (19.2±0.3μm). The probabilities of the regression coefficient being positive were 0.72 and 0.74 for implantation and birth, respectively, and the subsequent means of the coefficient were 2.92 and 0.03 for implantation and birth, respectively. In conclusion, the zona pellucida thickness has an important influence on in vivo fertilization and implantation processes, but not on birth.

Recurrent IVF failure: other factors

IVF failure is a problem for a couple in the singular but can be a tragedy in the plural. Recurrent IVF failure has multiple known causes but many which are not routinely considered as part of the posttreatment analysis. The reason is there are several causes associated with lifestyle and other causes related to pre-existing conditions that have only a tenuous or no apparent connection to fertility. This article examines the impact of obesity, cigarette smoke, uterine anatomy, body mass index, thyroid dysfunction, immune factors, the hereditary and acquired thrombophilias, and embryo transfer technique on recurrent IVF failure.

Detailed Analysis of Peripheral Blood Natural Killer Cells in Women with Repeated IVF Failure

To analyse the peripheral blood NK cells in women with repeated IVF failure (RIF) and a fertile control group to determine which parameters best differentiate the two populations. Peripheral blood from the luteal phase of 171 women with RIF and 33 fertile controls was analysed by four-colour flow cytometry for NK cell concentration, subset differentiation and the activation marker CD69. Women with RIF had significantly increased NK cell numbers as determined by concentration (P < 0.05) and percentage of lymphocytes (P < 0.001), increased concentration of the CD56(dim) subtype (P < 0.05), and increased concentration of activated CD56(dim) CD69(+) cells (P = 0.0001). There was no correlation between any NK cell parameters with the length of infertility or number of embryo transfer cycles. Peripheral blood NK cell activity is significantly higher in women with RIF than in fertile controls. Future trials of immune therapy in women undergoing IVF should target those with high NK activity.

Characterization of a recurrent poor-quality embryo morphology phenotype and zygote transfer as a rescue strategy

Some patients in IVF programmes repeatedly display an abnormal embryonic development characterized as soon as day 2 post fertilization by a high rate (>60%) of highly fragmented embryos (⩾40% of cytoplasmic fragments) leading to recurrent IVF failures. This study postulated that, for various maternal reasons, some embryos were unable to withstand the in-vitro environment and an early pronucleate-stage transfer was proposed to these couples. Fifty-three patients with recurrent IVF failures (a mean of 2.8±1.0 previous attempts) characterized by low embryonic quality (a mean of 62.7% of the embryos with extended fragmentation) were included this transfer protocol. As in previous cycles, the mean number of oocytes retrieved and the fertilization rate were normal. The mean number of zygotes per transfer was 2.24. Fourteen clinical pregnancies were obtained, representing a pregnancy rate and a delivery rate per oocyte retrieval of 26.4% and 18.9%, respectively. Recurrent heavy and early embryo fragmentation in vitro characterizes around 3% of IVF couples and leads to lack of transfer or implantation failure. These data on fresh zygote transfers are encouraging and may provide a valid alternative solution for some of these patients.Some patients in IVF programmes repeatedly display an abnormal embryonic development characterized as soon as day 2 post fertilization by a high rate of highly fragmented embryos, leading to recurrent IVF failures. We hypothesized that, for various reasons, some embryos were unable to withstand the in-vitro environment and an early pronucleate stage transfer was proposed to these couples. Fifty-three patients with recurrent IVF failures characterized by low embryonic quality were included in this transfer protocol. As in previous cycles, the mean number of oocytes retrieved and the fertilization rate were normal. The mean number of zygotes per transfer was 2.24. Fourteen clinical pregnancies were obtained, representing a pregnancy rate and a delivery rate per oocyte retrieval of 26.4% and 18.9%, respectively. Recurrent early and heavy embryo fragmentation in vitro characterizes around 3% of IVF couples and leads to lack of transfer or implantation failure. Our data on fresh zygote transfers are encouraging and may provide a valid alternative solution for these patients.

Assessment of 19,803 Paired Chromosomes and Clinical Outcome from First 150 Cycles using Array CGH of the First Polar Body for Embryo Selection and Transfer

Background: Meiosis 1 errors are believed to be the largest single cause of clinical embryo failure and early miscarriage. Following the failure of FISH technology and concerns over embryo mosaicism, our aim was to assess paired chromosome status and error rates, and predict oocyte aneuploidy using the metaphase2 polar body with a novel Array CGH platform as a means to select embryos for couples with multiple IVF failures. Methods: The PB1 was removed from metaphase 2 oocytes using a laser-assisted breech of the zona pellucida to effect the biopsy. Reliable 23-paired chromosome analysis was obtained, and in time for fresh embryo transfer. It was a non- randomised investigation in patients seeking this technology as a result of previous multiples failures of IVF. Results: 134 couples presented for 150 cycles of array CGH with a median age of 41.0. 861 polar bodies were evaluated, 67.4% and 32.6% were aneuploid and euploid, respectively. 19,803 paired chromosomes were analysed, 3.5% and 3.4% of chromosome errors resulted in either a gain or loss, respectively. There was a positive correlation between female age and aneuploidy, but no correlation with numbers oocytes harvested. 26% of cycles (n=39) failed to achieve embryo transfer (ET) as none of the oocytes were euploid. The live birth rate per ET and implantation was 24.1% and 27.7%, respectively, and 5.2% of chemical pregnancies (1.9% of transfers) resulted in a dizygotic multiple pregnancy. Conclusion: Array CGH was proven to generate robust chromosome information. Chromosome segregation error rates were found to be inversely proportional to chromosome length and proportional to the G/C base content. Clinically, the transfer of a single embryo after PB 1 array CGH analysis appeared to generate improved implantation rates in women with very poor prognosis, whilst reducing the risk of a multiple pregnancy.

Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure

Intrauterine administration of autologous peripheral blood mononuclear cells (PBMC) activated by HCG in vitro are reported to improve implantation rates in patients with repeated failure of IVF-ET. In this study, we examined the effects of intrauterine administration of freshly isolated PBMC on clinical pregnancy and the implantation rates of patients who received frozen/thawed embryo transfer by prospective cohort study. Patients who had not achieved a successful pregnancy despite at least one or more IVF-ET sessions were enrolled in this study (n = 253, 253 cycles). Based on the patient's treatment preferences, PBMC were freshly isolated from each patient and then administered to the intrauterine cavity of that patient. Frozen/thawed embryo transfer was performed and the success of implantation in the PBMC-treated group (n = 83, 83 cycles) was compared with that in the non-treated control groups (n = 170, 170 cycles). There were no significant differences in the clinical pregnancy rate (34.9% vs. 32.9%), implantation rate (21.6% vs. 21.1%) and live birth delivery rate (21.7% vs. 21.8%) between PBMC-treated and non-treated groups. However, when the analyses were restricted to patients who had three or more implantation failures, the clinical pregnancy rate and the implantation rate in the PBMC-treated group (42.1% and 25.0%, p<0.05; n = 19 and 32, respectively) were significantly higher than those in the non-treated group (16.7% and 9.4%, p<0.05; n = 36 and 64, respectively). These findings indicate that intrauterine administration of autologous PBMC freshly isolated from patients, effectively improves embryo implantation in patients with three or more IVF failures.

Effet du tabagisme sur l’implantation embryonnaire et la placentation précoce et facteurs influençant la toxicité tabagique sur la reproduction (Partie II)

Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was first to focus on the knowledge of the effects of cigarette smoking on reproductive stages and particularly on implantation process and early placentation. Human clinical and experimental studies were analysed in order to find hypothesis and explanations for the effects observed. Then, our second aim was to analyse which factors could influence smoke effects. We observed that smoke compounds induce impairment of endometrial maturation, disturb angiogenesis and trophoblastic invasion. Cigarette compounds also impair uterine and endometrial vascularisation and myometrial relaxation. These effects lead to implantation failure in IVF and higher risk of miscarriage. Many factors influence the effects of cigarette smoke, as smoke behaviour, dose and duration of exposition. Sidestream is also damaging on reproductive function. Prenatal exposure leads to irreversible and deleterious effects on ovarian reserve. These observations need to be confirmed in order to improve health care in women of reproductive age.