History Of Implantation Failure Research Articles

A pilot study of the intrauterine non-ablative erbium laser effectiveness in the endometrium preparation for cryopreserved embryo transfer in women with a history of implantation failures

Background. Embryo implantation failure remains an urgent issue of assisted reproductive technologies (ART).
 Aim. To determine the effect of intrauterine irradiation with a non-ablative erbium laser on the endometrium state using the histological and immunohistochemical examination and to evaluate its effectiveness in ART cryo-protocols.
 Materials and methods. The study enrolled 25 women aged 2645 with 1 to 5 failed implantations who were planning a pregnancy in a cryopreserved embryo transfer protocol. On days 610 of the menstrual cycle, all patients underwent a single procedure of intrauterine irradiation of the endometrium and cervical canal mucosa with an erbium laser in a non-ablative mode using Fotona SP Dynamis laser system (Slovenia). The histological and immunohistochemical data of the endometrium before and 12 months after the procedure and the pregnancy rate with subsequent transfer of the cryopreserved embryo were assessed.
 Results. Intrauterine irradiation with a non-ablative erbium laser increased the proliferative activity of the endometrium (p=0.029), the expression of vascular endothelial growth factor (p=0.029), reduced the sclerosis lesions in the spiral arteries and endometrial stroma, increased the expression of progesterone and estrogen receptors, thus significantly increasing the effectiveness of the ART cryo-protocols (p=0.013).

An In Vivo Screening Model for Investigation of Pathophysiology of Human Implantation Failure.

To improve current infertility treatments, it is important to understand the pathophysiology of implantation failure. However, many molecules are involved in the normal biological process of implantation and the roles of each molecule and the molecular mechanism are not fully understood. This review highlights the hemagglutinating virus of Japan (HVJ; Sendai virus) envelope (HVJ-E) vector, which uses inactivated viral particles as a local and transient gene transfer system to the murine uterus during the implantation period in order to investigate the molecular mechanism of implantation. In vivo screening in mice using the HVJ-E vector system suggests that signal transducer and activator of transcription-3 (Stat-3) could be a diagnostic and therapeutic target for women with a history of implantation failure. The HVJ-E vector system hardly induces complete defects in genes; however, it not only suppresses but also transiently overexpresses some genes in the murine uterus. These features may be useful in investigating the pathophysiology of implantation failure in women.

Co-administration of tacrolimus and low molecular weight heparin in patients with a history of implantation failure and elevated peripheral blood natural killer cell proportion.

To investigate the therapeutic effect of co-administration of tacrolimus (TAC) and low-molecular-weight heparin (LMWH) or LMWH only on pregnancy outcomes in the female with a history of implantation failure and elevated peripheral blood natural killer (pNK) cell proportion in frozen-thawed embryo transfer cycles. To evaluate the pregnancy parameters for 249 patients with ≥2 implantation failures and pNK cell proportion ≥12% by analyzing a retrospective observational cohort study. Sixty patients had received the co-administration TAC and LMWH (TAC & LMWH group), 85 others had only taken LMWH (LWMH group), and the rest did not take any particular drugs (control group). The experimental finding indicated that the TAC & LMWH group and the LMWH group showed higher clinical pregnancy rates than the control group (p < 0.05), and TAC & LMWH group had a much higher live birth rate. According to the binary logistic regression analysis, the combination of TAC and LMWH was conducive to clinical pregnancy and live birth rate and reduced the possibility of miscarriage. It would not affect the result of spontaneous abortion and live birth, although the LMWH was only beneficial to clinical pregnancy. In addition, these findings were similar for these three groups' obstetrical and neonatal outcomes. The combination of TAC and LMWH can improve clinical pregnancy and live birth rates and reduce the risk of spontaneous miscarriage in patients with a history of implantation failure and elevated pNK ratio. LMWH is also beneficial to clinical pregnancy.

Comparing the effects of endometrial injury in the luteal phase and follicular phase on in vitro fertilization treatment outcomes.

Several studies have shown that endometrial injury improves clinical pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment with a history of implantation failure. However, endometrial injury can be performed in the follicular phase (FP) followed by embryo transfer in the same menstrual cycle or in the luteal phase (LP) before the embryo transfer cycle. This prospective cohort study was conducted from January 2015 to September 2021, and a total of 487 patients were included. All included patients had a history of a failed implantation cycle. They were divided into two groups: the FP group (N = 330), in which endometrial injury was performed on menstrual day 3-5, and the LP group (N = 157), in which endometrial injury was performed in the cycle preceding embryo transfer 7 days after ovulation. First, in unselected patients, the implantation rate and clinical pregnancy rate were comparable between the LP and FP groups. However, in patients with a history of ≥ 2 failed transfer cycles, the implantation rate was significantly higher in the LP group than in FP group (43.09% versus 33.33%, P = 0.03). Moreover, the clinical pregnancy rate was also significantly higher in patients in the LP group than in patients in the FP group (60.17% versus 46.15%, P=0.02). In addition, logistic regression analysis showed that endometrial injury in the LP group was an independent factor affecting clinical pregnancy outcome in patients with a history of ≥ 2 failed transfer cycles (aOR = 2.05, 90% CI:1.22-3.47, P=0.01). Endometrial injury improves pregnancy outcomes when performed in the luteal phase compared with the follicular phase in patients with a history of ≥ 2 failed transfer cycles but not in unselected patients.

Melatonin Receptor 1B Polymorphisms and Reproductive Failure – a Pilot Study

The present study aimed to investigate the possible associations between the melatonin receptor 1B (MTNR1b) genetic polymorphisms and the presence of reproductive disturbances due to spontaneous abortion and implantation failure leading to pregnancy loss. The patients group included 35 women presenting with one or more miscarriages and/or implantation failure. Another 36 healthy women without history of implantation failure or miscarriages and with at least one birth served as a control group. Genomic DNA was extracted and genotyping for the MTNR1b polymorphisms rs1562444, rs10830962 and rs10830963 was performed by PCR-RFLP analysis. The genotype distribution of the investigated MTNR1b polymorphisms in patients with reproductive failure did not differ significantly to the group of women with at least one birth (p &gt; 0.05 for all). Nevertheless, the presence of a haplotype rs1562444 AA rs10830962 GG was significantly less common in women with miscarriages or implantation failure than in women with at least one birth (2.9% vs. 22.2%, p = 0.028). We suggest that the haplotype might be protective against implantation failure and spontaneous miscarriage. Additionally, rs1562444 AA genotype was not found in women with recurrent pregnancy loss. Studies in larger populations are necessary to reveal the proper associations between different MTNR1b haplotypes, ovarian function and reproductive failure.

Receptivity-based uterine fibroid surgery: an updated systematic review of the evidence

Background: Analyzing expression patterns of receptivity genes is a minimally invasive diagnostic method to identify the underlying cause of subfertility in women with uterine fibroid with a history of implantation failure or recurrent pregnancy loss. This updated systematic review was designed to determine the molecular and genetic changes in the endometrium of women with fibroid and how myomctomy affect the outcome of spontaneous or assisted conception treatment. We also discussed the extent to which we should consider the effects of fibroids on endometrial receptivity when deciding whether or not to perform myomectomy. Methods: A total of 184 articles reached as a result of PubMed research and meeting the selection criteria, were evaluated. Of these, 28 full text articles on uterine leiomyoma and endometrium, leiomyoma and receptivity, fibroid and implantation, myomectomy and implantation, fibroid and genes, fibroid surgery and receptivity, fibroid and uterine peristalsis, fibroid and immune cell were evaluated. Results: The endometrium of subfertile women with fibroid appears to have a disease specific pattern according to the type of the fibroid. The response of the endometrium to a fibroid may vary depending on whether the fibroid is close or far from it. Leiomyomas that contribute to subfertility must be near to or in contact with the endometrium, as is the case for Types 0, 1 and 2 leiomyomas. The proximity to the endometrial cavity makes the effect of fibroid on the endometrium more pronounced. While Type 3 fibroid causes subfertility similar to submucosal fibroids, the subfertility-producing effects of Type 4 fibroids have not been clearly clarified. However, the fact that the fibroid is far from the cavity should not mean that it has no effect on the endometrium. The mechanical stress created by a Type 4 fibroid that is not connected to the endometrium may be converted into biological signal and disrupt receptivity. Data on whether myomectomy restores impaired receptivity are mostly based on clinical observations, and studies evaluating endometrial receptivity before and after myomectomy are very few. Conclusions: Analysis of receptivity genes in subfertile women with fibroid may assist the clinician in deciding whether or not to perform myomectomy. If it is determined whether fibroids affect receptivity other than their mechanical effects, the indications for myomectomy may expand or narrow.

Prevalence of peripheral blood natural killer cells ≥12% in women with recurrent implantation failure: study carried out in a private clinic of Mexico City

Objective: To report the incidence of Natural killer cells peripheral blood (pNK) ≥12% and his relationship with Recurrent Implantation Failure (RIF) in a population of Mexican women. Methods: Retrospective, cross sectional and observational study that included 74 women with history of RIF, which were subjected to a study to evaluate pNK cell levels in order to avoid complications in future pregnancies. 2 groups were formed: 1) Control and 2) RIF: women with a history of implantation failure and primary infertility (with no history of pregnancies or abortions). Results: Women in RIF were younger and had higher BMI, compared to the Control. Prevalence of patients with pNK cells ≥12% was statistically higher in RIF than in Control (66.6% vs 20%). RIF showed a significative increase of pNK≥1 cell concentration, compared to Control (12.9±4.6 vs 9.5±0.6, p=0.00). When only women with results of pNK ≥12% were evaluated, RIF showed a level numerically higher than that of the Control (16±1.8 vs 13.5±0.8). Conclusion: RIF may be the result of increased pNK concentrations and as observed in this study, slightly more than 60% of the Mexican population could be susceptible to abortions.

Evaluation of the effect of intrauterine injection of platelet-rich plasma on the pregnancy rate of patients with a history of implantation failure in the in vitro fertilization cycle.

ABSTRACTObjectives:Implantation failure is a major problem in reproductive medicine, and despite the various methods described for treatment, there is little consensus on the most effective method. This study was conducted to investigate the effect of intrauterine injection of platelet-rich plasma (PRP) on the pregnancy rate of patients with a history of implantation failure in the in vitro fertilization (IVF) cycle.Study Design:In this study, women attending the infertility clinic of Ali ibn Abi Taleb Hospital, who had a history of implantation failure and were candidates for frozen embryo transfer (FET), were examined in Zahedan (Iran) in 2019. The patients were divided into two groups of PRP recipients and the control group. IVF was performed routinely, and in the PRP-receiving group, an intrauterine injection was given 48 h before embryo transfer (ET). The number of gestational sacs, the rate of implantation, the frequency of chemical and clinical pregnancies as well as the frequency of abortion were compared in the two groups. The collected data were analyzed by the SPSS software version 21Results:Ninety patients with a history of implantation failure participated in the study, and finally, the information of 85 patients was studied. The frequency of chemical pregnancy was 40% in the experimental group, 27% in the control group, and regarding clinical pregnancy, 33% in the experimental group and 24% in the control group, but there was no significant difference between the two groups. The rate of implantation, the mean thickness of the endometrium, and the frequency of abortion did not differ significantly between the two groupsConclusion:In patients with endometrial thickness greater than 8 mm with a history of recurrent implantation failure, intrauterine injection of PRP had no effect on the fertility outcome.

Routine endometrial receptivity array in first embryo transfer cycles does not improve live birth rate

To compare the live birth rate between patients who undergo personalized embryo transfer (pET) after endometrial receptivity array (ERA) versus frozen embryo transfer (FET) with standard timing in first single euploid FET cycles. To report the rate of displacement of the window of implantation (WOI) in an infertile population without a history of implantation failure. Prospective cohort study of patients who underwent their first single euploid programmed FET. Private fertility clinic. Patients who underwent first autologous single euploid programmed FET between January 2018 and April2019. Endometrial biopsy with ERA followed by pET as indicated. Live birth rate and rate of receptive and nonreceptive ERA. A total of 228 single euploid FET cycles were included in our analysis. Of those, 147 (64.5%) were ERA/pET cycles, and 81 (35.5%) were standard timing FET cycles. Endometrial receptivity array was receptive in 60/147 (40.8%) and nonreceptive in 87/147 (59.2%) patients. Nonreceptive ERAs were prereceptive in 93.1% of cases. The live birth rate did not differ between patients who underwent FET with standard timing and patients who underwent ERA/pET, 45/81 (56.6%) and 83/147 (56.5%), respectively. Our data do not support the routine use of ERA in an unselected patient population undergoing first autologous single euploid programmed embryo transfer.

Recurrent pregnancy loss resulting in IVF (In Vitro Fertilization) series. Pathophysiologic mapping. A systematic review

Objective: Assiduous depiction of recurrent pregnancy loss (RPL) in patients after in vitro fertilisation (IVF). Material and Method: Women undergoing IVF treatment who had experienced two or more consecutive pregnancy losses before 20 weeks’ gestation with or without a history of implantation failure. Systematic review resulting in specific data bases such as Pub Med and Cochrane data base. Results: Factors associated with RPL after IVF consist mainly genetic origin (approx. 30%) due to aneuploid embryos, followed by thrombophilia and autoimmune factors. Mainly predisposition factors associated with high risk of recurrent miscarriages include obesity, advanced maternal age, anatomic defects of the uterus and endocrine disorders. On the contrary, 10-15% of cases of RPL represent idiopathic origin (Unexplained RPL). The evaluation of preimplantation genetic testing (PGT) remains a controversial entity. Conclusion: The aim of our study is focusing on the pathophysiologic mapping, presented in current literature, concerning RPL after IVF. Although IVF procedures, including assisted hatching, PGT and immunologic therapy have been suggested to improve live birth rates, their efficacy is controversial, since the factors related to RPL after spontaneous abortion or IVF do not reveal any statistic differences. Additionally, assisted reproductive technique (ART) cannot be supported as a treatment intervention for couples with unexplained RPL, due to the lack of adequate clinical studies.

Frequency of Sperm Aneuploidy in Oligoasthenoteratozoospermic (OAT) Patients by Comprehensive Chromosome Screening: A Proof of Concept.

Background:Embryonic aneuploidy usually results in implantation failure and miscarriage. Considering significantly high frequency of sperm aneuploidy reported in oligoasthenoteratozoospermia (OAT) using fluorescence in situ hybridization (FISH) in limited number of chromosomes and lack of comprehensive chromosome screening (CCS) in OAT, the aim of this study was applying CCS in OAT sperm and comparison of the results with FISH findings.Methods:Five OAT patients with normal blood karyotypes and history of implantation failure were included. The successfully amplified samples, each containing two sperm, were analyzed by array comparative genomic hybridization (aCGH). FISH was utilized mainly depending on the aneuploidies found by aCGH to assess their frequencies in total sperm population.Results:In aCGH for 30 sperm, aneuploidy was found in 66% of samples. Following the study of 4300 sperm by FISH, an average of 55.46% aneuploidy was observed. No pregnancy was resulted with normal partners.Conclusion:Using aCGH, some abnormalities were observed that are not typically considered in sperm FISH studies. Despite small sample size of the comprehensive study, like other similar studies, the frequency of aneuploidies was considerable and similar to FISH. Aneuploidies revealed by aCGH at single sperm resolution were different from sperm population detected by FISH. Considering high frequency of aneuploidy in OATs sperm, preimplantation genetic testing for aneuploidy (PGT-A) can be used for in transfer of chromosomally normal embryos.

Comparing endometrial receptivity array to histologic dating of the endometrium in women with a history of implantation failure

ABSTRACT For patients with recurrent implantation failure in IVF, histologic or transcriptomic testing of the endometrium during the mid-secretory phase is often considered. Histological dating of endometrial biopsies (Noyes criteria) can determine if endometrial morphology is consistent with the period of receptivity. Alternatively, endometrial tissue can be sent for a commercial Endometrial Receptivity Array (ERA) test which characterizes the gene expression of the endometrium using a panel of 238 genes that have been implicated in endometrial receptivity. This study aimed to compare the two tests to assess their concordance and to examine the ability of the ERA to successfully predict implantation and pregnancy in a subsequent personalized embryo transfer. A retrospective review was done of 97 patients with a history of implantation failure who underwent an ERA, 35 of whom had histologic dating on the same sample. ERA and histology were classified as ‘concordant’ when samples were receptive by both tests or non-receptive by both tests. The ERA result was then used to personalize the embryo transfer day, and pregnancy rates from the first subsequent frozen transfer cycle were analyzed. The results indicated that there is poor concordance between ERA and histological dating with only 40.0% agreement and a kappa (95%CI) = −0.18 (−0.50, 0.14). According to the ERA, 48.5% of biopsies were receptive, 47.4% were non-receptive and 2.01% were insufficient tissue for analysis. The clinical pregnancy rate in patients shown to be receptive by ERA was 26.7% and non-receptive was 22.5% following the subsequent personalized ET (p = 0.66). This study concludes that there is a high degree of discordance between histological dating of the endometrium and molecular analysis by ERA. There was no evidence of clinical benefit when embryo transfer was personalized according to ERA in patients with a history of implantation failure.

Routine Endometrial Receptivity Array In First Embryo Transfer Cycles Does Not Improve Live Birth Rate

To report the rate of displacement of the window of implantation (WOI) in an infertile population without a history of implantation failure, and to compare the rates of live birth between patients who undergo personalized embryo transfer (pET) after ERA versus FET with standard timing.

ART implantation failure and miscarriage in patients with elevated intracellular cytokine ratios: response to immune support therapy

BackgroundThe origins of adverse reproductive outcome can be multifactorial, but the contribution of the maternal immune system is considered debatable. Elevated intracellular cytokine ratios have been proposed, although not universally supported, as a marker for immunological dysfunction in implantation and early pregnancy. Poor patient selection or inadequate treatment or testing may be confounding factors. Specific immunomodulation, in carefully selected sub-populations of ART patients with poor reproductive history, despite transfer of good quality blastocysts, may potentially improve clinical outcomes.MethodsIntracellular cytokine ratios (CKR) were prospectively assessed in 337 patients presenting with a history of implantation failure and/or pregnancy loss, prior to further treatment, and were found to be elevated in 150 (44.5%). Of this group, 134 agreed to initiate a standardised immunotherapy regime (nutraceuticals, prednisolone & intralipids) to evaluate the efficacy of this proposed therapy. Of the intervention population, a small cohort (n = 70) delayed commencing ART for ~ 10 weeks to assess if extended pre-treatment nutraceutical supplementation could normalise CKRs prior to starting ART, and if this conferred additional benefit.ResultsBaseline assessment in the intervention population (n = 134) identified 160 miscarriages from 180 total pregnancies (89% miscarriage rate, MR), conceived both spontaneously and by assisted reproduction. Post-treatment analysis of subsequent ART cycles revealed a significant improvement in both implantation (OR 3.0, 2.0–4.5) and miscarriage rates (41/97, 42.2% MR, P < 0.001). Interestingly, pre-treatment normalisation of CKRs appeared to impart marginal extra benefit prior to subsequent fertility treatment with immunotherapy.ConclusionsFollowing immunomodulation, significant improvements in both implantation rate and miscarriage rate were seen in this poor prognosis population. This suggests a possible role for both detailed immuno-evaluation of patients with poor reproductive history with good embryo quality, and application of personalised immunotherapy regimes alongside ART in selected cases. Future randomised controlled trials are needed to definitively evaluate this potentially promising therapeutic approach.

Transcutaneous electrical acupoint stimulation (TEAS) treatment improves pregnancy rate and implantation rate in patients with implantation failure

ObjectiveAlthough major advances have greatly improved the outcomes of assisted reproductive technology in the last two cascades, there remains significant difficulty in achieving pregnancy for many patients even after repeated attempts of IVF. Interestingly, recent studies have shown that transcutaneous electrical acupoint stimulation (TEAS) can improve the reproductive outcomes of select IVF patients. To determine the utility of TEAS in improving IVF outcomes in patients with a history of implantation failure, we conducted a retrospective study of clinical outcomes of women, who had a prior history of unsuccessful pregnancy outcome after IVF-embryo transfer (IVF-ET), following TEAS treatment. Materials and methodsA total of 25 patients, who had failed to conceive after multiple IVF cycles in which good embryos were transferred, received noninvasive low frequency TEAS treatment prior to and during an IVF-ET cycle. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate and implantation rate, were compared to those of prior cycles which received only standard IVF treatment. ResultsAnalysis of reproductive outcomes showed that implantation rate and clinical pregnancy rate increased significantly in IVF cycles that included the TEAS treatment when compared to prior cycles that received only the standard IVF treatment in this cohort of patients. ConclusionsThis surprising finding indicated that TEAS treatment is a promising technique to improve reproductive outcomes in difficult cases of IVF-ET. Because TEAS treatment is noninvasive and has high reproducibility, and can be applied with limited training, further refinement of this procedure would not only substantiate the beneficial effects of TEAS, but also allow the technique to be more effective and reproducible.

Efficacy of Intrauterine infusion of granulocyte colony stimulating factor on patients with history of implantation failure: A randomized control trial

Although pregnancy rate in in vitro fertilization-embryo transfer (IVF-ET) cycles has been increased over the preceding years, but the majority of IVF-ET cycles still fail. Granulocyte colony stimulating factor (GCSF) is a glycoprotein that stimulates cytokine growth factor and induces immune system which may improve pregnancy rate in women with history of implantation failure. The aim of this study was to evaluate GCSF ability to improve pregnancy rate in women with history of implantation failure. 0.5 ml (300 µg/ml) GCSF was infused intrauterine in intervention group. Pregnancy outcomes were assessed based on clinical pregnancy. The mean age of participants was 31.95±4.71 years old. There were no significant differences between demographic characteristics in two groups (p>0.05). The pregnancy outcome in GCSF group was improved significantly (p=0.043). GCSF can improve pregnancy outcome in patients with history of implantation failure.

Repeated implantation failure versus repeated implantation success: discrimination at a metabolomic level.

Is there any difference at the serum metabolic level between women with recurrent implantation failure (RIF) and women with recurrent implantation success (RIS) when undergoing in vitro fertilization (IVF)? Eight metabolites, including valine, adipic acid, l-lysine, creatine, ornithine, glycerol, d-glucose and urea, were found to be significantly up-regulated in women with RIF when compared with women with RIS. Despite transfer of three high-grade embryos per cycle, RIF following three or more consecutive IVF attempts occurs in a group of infertile women. Conversely, there is a group of women who undergo successful implantation each cycle, yet have a poor obstetric history. This study was conducted over a period of 10 years (January 2004-October 2014). Groups of 28 women with RIF (age ≤40 years and BMI ≤28) and 24 women with RIS (age and BMI matched) were selected from couples with primary infertility reporting at the Institute of Reproductive Medicine, Kolkata, India. Women recruited in the RIF group had history of implantation failure in at least three consecutive IVF attempts, in which three embryos of high-grade quality were transferred in each cycle. Blood samples were collected from both the groups during the implantation window following overnight fasting for at least 10 h (7-10 days post ovulation). Samples were analyzed using a 700 MHz NMR spectrometer and acquired spectra were subjected to chemometric and statistical analysis. Serum levels of endothelial nitric oxide synthase (eNOS) were measured using an enzyme immunoassay technique. Valine, adipic acid, l-lysine, creatine, ornithine, glycerol, d-glucose and urea were found to be significantly down-regulated in women with RIS when compared with those with RIF, with fold change values of 0.81, 0.82, 0.79, 0.80, 0.78, 0.68, 0.76 and 0.74, respectively. Further, serum eNOS was found to be significantly lower in women with RIF when compared with RIS (P < 0.05), indicating possible impairment in nitric oxide production. Metabolites, mostly related to energy metabolism, lipid metabolism and the arginine metabolic pathway were found to be considerably altered and are likely to be associated with the RIF phenomenon. However, the interplay between these molecules in RIF is complex and holds merit for further exploration. In-depth studies of the arginine metabolic pathway in endometrial tissues seem necessary to validate our findings. A limitation of the present study is that the metabolic level changes, eNOS and nitric oxide levels have not been investigated in the endometrial tissues of the two groups of women. It would be interesting to investigate whether there exists a direct link between metabolic dysregulation and genetic factors that affects implantation in RIF women. We speculate that tissue metabolomics can provide an improved understanding of the metabolic dysfunction associated with RIF. The identification of serum metabolic marker(s) in women with RIS may help with strategies of early therapeutic intervention, which may improve the chances of implantation significantly in women otherwise susceptible to IVF failure. One of the authors, S.R.C. acknowledges the Council of Scientific and Industrial Research (CSIR), Government of India [No: 9/81(1228)/14, EMR-I] for financial support.

Does flushing the endometrial cavity with follicular fluid after oocyte retrieval affect pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection? A randomized controlled trial

ObjectiveFollicular fluid of mature oocytes is rich in growth factors and cytokines that may exert paracrine and autocrine effects on implantation. The aim of this study was to investigate if flushing the endometrial cavity with follicular fluid after oocyte retrieval improved pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection (ICSI). Study designOne hundred subfertile women undergoing ICSI between April 2012 and September 2012 at the centre for reproductive medicine, Cairo University, Egypt were enrolled in this open label, parallel randomized controlled study. Patients were randomized into two groups at the start of treatment using a computer-generated programme and sealed opaque envelopes: the follicular fluid group (n=50) and the control group (n=50). Inclusion criteria were: age 20–38 years; basal follicle-stimulating hormone <10mIU/ml; body mass index <35kg/m2; and ostradiol >1000pg/ml and <4000pg/ml on the day of human chorionic gonadotrophin administration. Exclusion criteria were: evidence of endometriosis; uterine myoma; hydrosalpinges; endocrinological disorders; history of implantation failure in previous in-vitro fertilization/ICSI cycles; and severe male factor infertility. ResultsClinical pregnancy and implantation rates were higher in the follicular fluid group compared with the control group [354% (17/48) vs 319% (15/47); p=0718] and (18.6% vs 11.3%; p=0.153), respectively. However, the difference was not statistically significant. ConclusionFlushing the endometrial cavity with follicular fluid after oocyte retrieval neither improved nor adversely affected clinical pregnancy and implantation rates in subfertile women undergoing ICSI.

Impact of active cycle endometrial biopsy on implantation and pregnancy rates in fresh IVF cycles in patients with history of implantation failure

Impact of active cycle endometrial biopsy on implantation and pregnancy rates in fresh IVF cycles in patients with history of implantation failure

Endometriosis and Assisted Reproductive Technologies: Maximizing Outcomes

In vitro fertilization (IVF) represents the most efficient means of overcoming endometriosis-related infertility. Compromised pelvic anatomy and a hostile peritoneal environment are bypassed. Despite the results of early trials, more contemporary outcomes data would suggest that when controlled for age, IVF cycle outcome is not compromised by the presence of endometriosis. One exception to this concept is the finding that patients with ovarian endometriomas demonstrate poorer response to gonadotropin therapy, although it is not clear that this affects the likelihood of implantation. Surgical ablation of superficial endometriosis has no clear impact on IVF pregnancy rates, although a small number of recent trials suggest that pre-cycle resection of deeply infiltrative disease may be beneficial. With the exception of traditional gynecologic indications, there is no evidence to suggest that resection of ovarian endometriomas has any positive impact on cycle outcome. There are, in fact, data demonstrating that resection may exert a deleterious effect on ovarian reserve. A subset of patients will benefit from administration of a prolonged course of a gonadotropin-releasing hormone agonist prior to an IVF cycle. However, the characteristics of that subset have not been identified. It would be logical to consider this approach in women with more advanced disease, severe symptoms, and a history of implantation failure. Data on the impact of other pre-cycle medical interventions such as aromatase inhibitors, danazol, or oral contraceptives are more limited. There is also no evidence to suggest that the ovarian stimulation associated with IVF induces progression of endometriosis.