IVF Failure Research Articles

Excision of adenomyosis in the setting of recurrent IVF failure

Excision of adenomyosis in the setting of recurrent IVF failure

High accuracy machine learning predictive model for embryo selection in IVF PGT cycles with single embryo transfers

Recent publications have demonstrated significant improvement in IVF treatment outcomes by implementing NGS-based preimplantation genetic testing (PGT) while transferring fewer embryos. The objective of this study was to create complex machine learning (ML) model that can accurately predict the reproductive potential of a particular euploid embryo to establish viable pregnancy in IVF PGT cycles with single embryo transfer (SET). A retrospective study of NGS PGT outcome data from blastocysts biopsied on day 5 or day 6 (2013-2017) was conducted using supervised and unsupervised ML algorithms to identify differences in clinical pregnancy rates (PR). 1383 cycles (7120 embryos) of IVF PGT followed by 1108 SETs were included in the study (842 patients). From 320 original features (175 clinical and 145 morph. and kinetic parameters of embryo development), 6470 synthetic features were created (by Weight of Evidence, Encoding of categorical levels, Target Encoding, etc.), tested and 357 features were selected. 73 statistical models were trained and ensembled in the final model. Predictive accuracy was evaluated by 5-fold cross-validation. Clinical PR was defined by the presence of a fetal heartbeat at 6-7 weeks of pregnancy. Analysis of the combined predictions from multiple weak learners (GLM, random forest, gradient boosting, etc.) processed by Generalized Model Stacking produced a predictive performance of AUC = 0.8103, Logloss = 0.5356. The probability of positive clinical outcome was calculated for each euploid embryo and ranged from 0.194 to 0.838 (baseline prediction - 0.645). The variable of highest importance were the morphological characteristics of the blastocysts, the history of previous failed IVF cycles, and time when blastocysts became available for biopsy (0.372, 0.233, and 0.118 respectively). Generalized linear model intercept estimate for embryo morphology was 0.957 (Std. Error = 0.36, Pr (|z|) = 0.008), intercept estimate for the history of previous failed IVF cycles was -0.625 (Std. Error = 0.1, Pr (|z|) = 3.1e-10), and intercept estimate for biopsy day was -0.416 (Std. Error = 0.133, Pr (|z|) = 0.002). These results were confirmed by univariate analysis: the ongoing PR after SET was considerably higher when the transferred euploid embryos were graded as good quality embryos (AA/AB/BA) vs fair (BB) or borderline fair (-B or B-) quality: 68.6% (493/719) vs 56.9% (161/283) and 42.5% (45/106) respectively, χ2=4.31, OR = 0.338, CI = 0.223 - 0.513, p<0.05. Analysis of the data proved that Machine learning algorithms applied to large clinical data sets could predict the outcome of the IVF treatment with high accuracy. In order to achieve high accuracy predictions in IVF PGT cycles factors affecting clinical outcomes were defined, ranked, and evaluated. Ensemble methods of statistical learning offer superior performance over their singleton counterparts and essentially help to transform medical records into medical knowledge.

Preimplantation genetic diagnosis versus prenatal diagnosis—decision-making among pregnant FMR1 premutation carriers

To detect which factors influence decision-making among pregnant FMR1 premutation carriers regarding the preferred mode of genetic diagnosis: IVF-PGT-M (in vitro fertilization with preimplantation genetic testing for monogenic gene diseases), or CVS (chorionic villus sampling), or AC (amniocentesis) after spontaneous conception. In Israel FMR1 premutation preconception genetic screening is offered, free of charge, to every woman in her reproductive years. FMR1 premutation carriers with ≥70 CGG repeats, or a history of FXS offspring, are offered IVF-PGT-M. This is a historical cohort study including all pregnant FMR1 premutation carriers who underwent prenatal diagnosis between the years 2011 and 2016 at a tertiary medical center. Data were collected from electronic charts and through phone interviews. One hundred seventy-five women with high-risk pregnancies who were offered IVF-PGT-M were evaluated. In 37 pregnancies (21%), the women decided to undergo IVF-PGT-M. Using the generalized estimating equations (GEE) statistical method including seven parameters, we found that previous termination of pregnancy due to FXS and advanced woman's age were significantly associated with making the decision to undergo IVF-PGT-M. Previously failed IVF was the most significant parameter in a woman's decision not to undergo IVF-PGT-M. The most dominant factor affecting the decision of FMR1 premutation carriers to choose spontaneous conception with prenatal diagnosis versus IVF-PGT-M is a previous experience of failed IVF treatments. Women whose IVF treatments failed in the past tended to try to conceive naturally and later, during the course of the pregnancy, perform CVS or AC. Conversely, women who previously experienced a termination of pregnancy (TOP) due to an affected fetus, and older women, preferred to undergo IVF-PGT-M procedures.

Enhanced Differentiation Potential of Primary Human Endometrial Cells Cultured on 3D Scaffolds.

Novel approaches for culturing primary human cells in vitro are increasingly needed to study cell and tissue physiology and to grow replacement tissue for regenerative medicine. Conventional 2D monolayer cultures of endometrial epithelial and stromal cells fail to replicate the complex 3D architecture of tissue. A fully synthetic scaffold that mimics the microenvironment of the human endometrium can ultimately provide a robust platform for investigating tissue physiology and, hence, take significant steps toward tackling female infertility and IVF failure. In this work, emulsion-templated porous polymers (known as polyHIPEs) were investigated as scaffolds for the culture of primary human endometrial epithelial and stromal cells (HEECs and HESCs). Infiltration of HEECs and HESCs into cell-seeded polyHIPE scaffolds was assessed by histological studies, and phenotype was confirmed by immunostaining. Confocal microscopy revealed that the morphology of HEECs and HESCs is representative of that found in vivo. RNA sequencing was used to investigate transcriptome differences between cells grown on polyHIPE scaffolds and in monolayer cultures. The differentiation status of HEECs and HESCs grown in polyHIPE scaffolds and in monolayer cultures was further evaluated by monitoring the expression of endometrial marker genes. Our observations suggest that a 3D cell culture model that could approximate native human endometrial architecture and function can be developed using tailored polyHIPE scaffolds.

PGS: a four-letter word?

Preimplantation genetic screening (PGS) involves the identification of chromosome abnormalities in IVF embryos (rather than targeting diagnosis to a specified gene). Chiefly employed for couples with advanced maternal age, recurrent miscarriage or recurrent IVF failure, it aims to improve IVF success, and reduce miscarriage and affected live birth rates. The process involves the sampling of cells by embryo biopsy, cytogenetic diagnosis, then selective transfer of an apparently chromosomally normal embryo in the hope of establishing a pregnancy. Although PGS is the most common variant of PGD (preimplantation genetic diagnosis), accounting for 80% of cases it has, from the outset, been one of the most controversial areas of reproductive medicine. The subject of intense debate, it attracts opinions ranging from recommendations that it should be applied in all IVF cases, through to the suggestion it should be discontinued completely. What do you think? Should it continue or not?

The influence of endothelial cell protein C receptor gene 6936A/G, 1651C/G, 4678G/C polymorphisms and soluble endothelial protein C receptor levels on in vitro fertilization outcomes

Hypercoagulability could be intrinsic or caused by the hormone treatment preceding the IVF procedure. Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C by the thrombin–thrombomodulin complex. Soluble EPCR plays a role in the maintenance of pregnancy evidenced by the findings that EPCR expression is critical for embryo development. Specific gene variants linked with altered soluble EPCR levels were associated with poor pregnancy outcome. The aim of this study was to assess the predictive value of EPCR gene polymorphisms (6936A/G, 1651C/G, and 4678C/G) and sEPCR level on the IVF outcome in Egyptian women with repeated IVF failure. They were compared to healthy control patients eligible for IVF. The present study was conducted on 45 women with repeated IVF failure, three or more previous IVF-embryo transfer cycles, and 45 healthy age-matched women eligible for IVF. PCR-RFLP for the EPCR polymorphisms (6936A/G, 1651C/G, 4678G/C) was done for cases and control groups. Plasma-soluble EPCR levels were measured with ELISA. As regards the mutant, EPCR (6936A/G) genotypes (AG, GG) were higher than the wild type (AA) (P < 0.001, OR 4.125, 95% CI 2.198–7.740). The homozygous mutant genotype (GG) was higher in comparison to the wild type (AA). The mutant allele (G) was higher than the wild allele (A) (P < 0.001, or 2.549, 95% CI 1.601–4.061). Higher frequencies of the (1651C/G) genotype and lower soluble EPCR levels were noted both in (C/C) (P = 0.004; Z = −0.2867) and (C/G) (P = 0.006; Z = −0.2767) genotype carriers. Regarding, EPCR polymorphism (4678G/C), the homozygous mutant genotype (CC) was significantly lower than the homozygous wild type (GG), (P = 0.014, OR 0.289, 95% CI 0.108–0.776). Our data suggest that the 6936A/G and 1651C/G EPCR gene variants coupled with procoagulant diminished levels of sEPCR may be associated with a higher tendency for repeated implantation failure.

Stress, anxiety, and depression of both partners in infertile couples are associated with cytokine levels and adverse IVF outcome.

Psychiatric disorders and stress in women have been associated with poor IVF outcome. We hypothesized that both partners in the infertile couples are emotionally affected, and cytokines in both may link psychological to reproductive outcome. Forty-five IVF couples completed questionnaires and visual analog scales for stress and psychiatric disorders and had cytokines measured in serum, semen, cervicovaginal, and follicular fluids. Multivariable analyses, t tests, maximum likelihood estimates, Spearman correlation, and data mining were applied. Psychopathology was found in 72% of the couples. Female and male stress were associated with stress, anxiety, and depression in the respective partner, and with a lower likelihood of clinical pregnancy and live birth. Lower serum TGF-β and higher cervicovaginal IL-6 and IL-1β were associated with stress. In data decision trees, cytokines in relation to stress and depression in both partners were found indicative of IVF failure. Infertile couples may benefit from psychiatric evaluation and treatment of both partners.

Higher than expected reproductive risk for autosomal paracentric inversion carriers

Introduction: Autosomal paracentric inversions are generally considered to be harmless without phenotypic effect in carriers, but recombination can occur during gametogenesis causing genetically unbalanced gametes and embryos. If a recombinant gamete is formed following a crossover in the inverted segment, the chromosome would be either acentric or dicentric. The resulting embryo will be unbalanced. This could lead to repeated IVF failures or repeated pregnancy loss, frequently seen among inversion carriers as well as a possible affected child. Previous studies performed in sperm of autosomal paracentric inversion carriers show recombination is scarcely ever seen (0–0.81% of recombinants in 5 cases) with the exception of one sperm FISH study showing 28% of recombinant gametes. The main goal of this study is to retrospective analyze the results of PGD performed in autosomal paracentric inversion carriers, in order to see the number and frequency of unbalanced embryos and its possible relationship with the inversion size.

Clinical and Anamnestic, Immunological, Echographic, and Hysteroscopic Features of Chronic Endometritis Associated with Impaired Reproductive Function

Background: The widespread prevalence of infertility, the low effectiveness of assisted reproductive technologies (ART), and the high incidence of chronic endometritis (CE) in infertile women determine the relevance of the considered problem. The aim of the study was to determine the clinical and anamnestic, laboratory, and instrumental features of CE associated with infertility and unsuccessful IVF cycles in women of reproductive age. Materials and methods: The study enrollred 150 women of reproductive age with morphologically established CE (main group, n=120) and without CE (control group, n=30). A subgroup I of the main group included 64 patients with infertility and IVF failures, a subgroup II – 56 fertile women. In addition to anamnesis collection and identification of CE clinical features, all patients underwent infectious screening, immunological and immunohistochemical analysis, ultrasound examination of pelvic organs with dopplerometry, and office hysteroscopy. A comparative analysis of the data obtained from subgroups of the main group was conducted. Results: Histological study of endometrial pipelle-biopsy specimens on the 7−10th day of the cycle revealed CE in all patients of the main group. We found prevalence of mean duration of CE in the subgroup I relative to subgroup II ― 5.5±0.06 years and 2.4±0.07 years, respectively (p0.001). Infectious screening showed that 58 (90.6%) patients of the I subgroup had sterile endometrial seeding which was 16.9 times higher than in subgroup II (p0.0001). Immunological analysis determined the presence of AEAT in all patients of the subgroup I, 43 of which (67.2%) were above 265 U/ml, while 51 (91.1%) of subgroup II had no AEAT (p0.001). Immunohistochemical analysis of the endometrium on the 18th−24th day of the cycle established high expression of CD16 , CD20 , CD56 , and HLA-DRII in 58 (90.6%) patients of the subgroup I, whereas in 54 patients (96.4%) of II subgroup high expression of CD16 and CD20 with low amount of CD56- and HLA-DRII-positive cells was registered (p0.001). We determined prognostically significant clinical and anamnestic risk factors predisposing to the development of infertility in patients with CE (p0,05). We revealed certain echographic, dopplerometric, and hysteroscopic criteria of CE demonstrating the critical disruption of endometrial receptivity in infertile women. Conclusion: Most patients (90.6%) with infertility had autoimmune component of CE characterized by prolonged (more than 5 years) course, high serum level of AEAT, sterile endometrial crops, and high expression of inflammation markers CD16 , CD20 , CD56 and HLA-DRII .

HYSTEROSCOPY BEFORE IN VITRO FERTILIZATION

In the last decade, success after in vitro fertilization process (IVF) has remained at a similar rate despite all the improvements implemented in the stimulation protocols and laboratory techniques. Hysteroscopy is a method becoming more widely used with patients after a failed IVF cycle, considering a large incidence of uterus cavum pathological states which have a negative impact on the favorable outcome. Numerous studies have provided different results on the IVF outcome with hysteroscopy performed prior to this treatment in cases with no uterus cavum pathology. The aim of the research was to examine the effect of both diagnostic and surgical hysteroscopy on the outcome of IVF. Hysteroscopy was performed with 74 patients 30 to 50 days prior to IVF and in 33 of them (group I) some pathological state was noticed, which was treated during the same procedure. The control group (group III) included 151 patients who had IVF performed with no prior hysteroscopy. There is no statistically significant difference in the rate of post hysteroscopy implantation between I and II group when compared to the control group (20.62% vs 23.28% vs 17.31%), nor in the rate of clinical pregnancies (45.45% vs 46.34% vs 34.44%). Following the correctional treatment of uterus cavum pathological states, implantation and pregnancy rates remain at a level comparable to hysteroscopically normal medical findings. Statistically significant higher pregnancy rate is present in group I after the first IVF cycle, compared to the next IVF in the same group and in comparison to the next IVF cycle in the control group (60.00% vs 27.91%, p&lt;0.05). Hysteroscopy is a simple and safe method allowing nearly identical rate of clinical pregnancies after a surgical treatment of uterus cavum pathological states when compared to the control group, but statistically much higher pregnancy rate if the order of IVF procedure is being compared. In cases of normal ultrasound findings and negative hysteroscopical findings, performing hysteroscopy prior to IVF does not provide significantly better results. Therefore, its routine execution is not recommended.

Window of Implantation is Significantly Displaced in Patients with Adenomyosis with Previous Implantation Failure as Determined by Endometrial Receptivity Assay.

Background:Adenomyosis is associated with implantation failure and poor reproductive performance in IVF/ICSI cycles.Aims:To compare if window of implantation (WOI) is displaced in patients having adenomyosis compared to controls using endometrial receptivity array (ERA) test.Settings and Design:Retrospective Case control study. 374 patients with previous one or more IVF failures who underwent ERA test between 2013-2016 at our centre were enrolled. Patients were divided into two groups; Group A-36 patients with adenomyosis (study group) and Group B- 338 patients without adenomyosis (controls).Statistical Analysis:Normality assumptions for continuous variables were tested using Kolmogorov Smirnov test. Mean values of two groups were compared using Student's t-independent test. Frequency data by categories were compared using Chi-square/Fisher's exact test. Risk ratio and 95% confidence limits were calculated. P < 0.05 was considered for statistical significance.Results:WOI was displaced (Non Receptive ERA) significantly in adenomyosis 47.2% (17/36) compared to controls 21.6% (73/338) (P < 0.001, CI-8.7%-42.5%) making risk ratio of displaced WOI in adenomyosis versus controls to be 2:1. The incidence of RIF was 66.6% in adenomyosis compared to 34.9% in controls (P < 0.001, CI- 15.5%-47.9%). Pregnancy rate after personalized embryo transfer in adenomyosis group was 62.5%, signifying displaced WOI as a cause of implantation failure in adenomyosis patients with previous implantation failure.Conclusions:Our study suggests it is prudent to evaluate Endometrial receptivity before embryo transfer in patients with adenomyosis to avoid wastage of good embryos.

Does using testicular sperm retrieval rather than ejaculated spermatozoa improve reproductive outcomes in couples with previous ART failure and poor ovarian response? A case-controlled study.

The objective of this study was to assess whether testicular-retrieved spermatozoa improve reproductive outcomes compared to fresh ejaculate in women with poor ovarian response and a history of previous ART failure. The study was performed as a retrospective case-control study at a university-based reproductive center in Montreal, Quebec, Canada. Eighteen poor-responder patients were matched 3:1 with 54 controls. Poor responders were defined as those with ≤3 oocytes retrieved at oocyte pickup. Cases were identified as poor responders, and only those with previous IVF failure(s) as an indication for testicular-retrieved spermatozoa were included. Controls were age and cycle attempt number matched. All patients were included only once. From January 1, 2009 to December 31, 2015, all patients and controls underwent an IVF cycle using ICSI with either testicular spermatozoa or ejaculated spermatozoa, respectively. Outcomes included live birth rate, pregnancy rate, miscarriage rate, oocyte number, and embryo transfer (ET) day. The results showed live birth rates, pregnancy rates, and miscarriage rates were similar. There were fewer day 2 ETs (8.5% vs. 48.6%, p=0.01) and more day 5 blastocyst transfers (25.0% vs. 5.4%, p=0.05) in the testicular sperm retrieval group compared to controls and thus an overall suggestion of better embryo quality in the testicular sperm group. Overall, however, the use of testicular sperm retrieval appears to add little. Women with poor ovarian response typically have a poor prognosis with respect to live birth rates, and this is further supported in this study. The suggestion of better embryo quality in the testicular-retrieved sperm group would need to be further assessed in a larger multicentered study.

A novel method of sperm immobilization test applied with computer-aided sperm analysis (CASA)

Thyroid autoimmunity (TAI) appears to play a crucial role in female infertility, recurrent pregnancy loss and IVF failure. Thyroid autoantibodies against thyroid peroxidase and thyroglobulin have been shown to represent an independent risk factor for infertility and miscarriage. Moreover, thyroxin hormone administration reduces the risk of obstetrical complications in TAI positive women.The aim of our present study was to investigate the immunological background of female infertility and recurrent pregnancy loss in euthyroid and subclinical hypothyroid women with TAI focusing on innate immunity.Phenotypic and functional analysis was carried out on peripheral blood mononuclear cells from healthy donors and TAI patients by flow cytometry. Our findings show Th1 oriented changes of innate immunity in the peripheral blood of women suffering from thyroid autoimmunity. Elevated NK and NKT-like cells ratios and enhanced natural cytotoxicity of TAI positive women reveal an altered immune status with possible negative impact on pregnancy outcome. It is important to notice that immune alterations are already established in the euthyroid phase of autoimmune thyroiditis before endocrine dysfunction develops and only the presence of thyroid autoantibodies indicate TAI condition.For this reason, screening of healthy women of reproductive age for the presence of thyroid autoantibodies would be beneficial not only from the endocrinological aspect but from the reproductive point of view since, although yet unexplained, thyroid hormone administration may improve pregnancy outcome.

A case of Asherman's syndrome due to genital tuberculosis

Thyroid autoimmunity (TAI) appears to play a crucial role in female infertility, recurrent pregnancy loss and IVF failure. Thyroid autoantibodies against thyroid peroxidase and thyroglobulin have been shown to represent an independent risk factor for infertility and miscarriage. Moreover, thyroxin hormone administration reduces the risk of obstetrical complications in TAI positive women.The aim of our present study was to investigate the immunological background of female infertility and recurrent pregnancy loss in euthyroid and subclinical hypothyroid women with TAI focusing on innate immunity.Phenotypic and functional analysis was carried out on peripheral blood mononuclear cells from healthy donors and TAI patients by flow cytometry. Our findings show Th1 oriented changes of innate immunity in the peripheral blood of women suffering from thyroid autoimmunity. Elevated NK and NKT-like cells ratios and enhanced natural cytotoxicity of TAI positive women reveal an altered immune status with possible negative impact on pregnancy outcome. It is important to notice that immune alterations are already established in the euthyroid phase of autoimmune thyroiditis before endocrine dysfunction develops and only the presence of thyroid autoantibodies indicate TAI condition.For this reason, screening of healthy women of reproductive age for the presence of thyroid autoantibodies would be beneficial not only from the endocrinological aspect but from the reproductive point of view since, although yet unexplained, thyroid hormone administration may improve pregnancy outcome.

Are blastocyst aneuploidy rates different between fertile and infertile populations?

This study aimed to determine if patients with infertility or recurrent pregnancy loss have higher rates of embryo aneuploidy than fertile controls. This was a retrospective review of all pre-implantation genetic screening (PGS) cases processed by a single reference lab prior to March 2014 after a blastocyst biopsy. Cases were excluded if no indication for PGS was designated or patients were translocation carriers. The fertile control group consisted of patients undergoing IVF with PGS for sex selection only. The comparison cohorts included those with recurrent pregnancy loss, male factor infertility, unexplained infertility, prior failed IVF, or previous aneuploid conceptions. A quasi-binomial regression model was used to assess the relationship between the dependent variable, aneuploidy rate and the independent variables, maternal age and reason for PGS. A quasi-Poisson regression model was used to evaluate the relationship between similar independent variables and the number of blastocyst biopsies per case. The initial study population consisted of 3378 IVF-PGS cycles and 18,387 analyzed trophectoderm samples. Controlling for maternal age, we observed an increased rate of aneuploidy among patients with recurrent pregnancy loss (OR 1.330, p<0.001), prior aneuploid pregnancy (OR 1.439, p<0.001), or previous failed IVF cycles (OR 1.356, p=0.0012) compared to fertile controls. Patients with unexplained and male factor infertility did not have a significantly different aneuploidy rate than controls (p>0.05). The increase in aneuploidy in patients with RPL and prior IVF failure was driven by both an increase in meiotic (OR 1.488 and 1.508, p<0.05) and mitotic errors (1.269 and 1.393, p<0.05) relative to fertile controls, while patients with prior aneuploid pregnancies had only an increased risk of meiotic error aneuploidies (OR 1.650, p<0.05). Patients with recurrent pregnancy loss, previous IVF failures, and prior aneuploid pregnancies have a significantly higher, age-independent, aneuploidy rate compared to patients without infertility.

Effect of Sildenafil Citrate on the Outcome of in Vitro Fertilization after Multiple IVF Failures Attributed to Poor Endometrial Development : A Randomized Controlled Trial

Aim of the work: this study aimed to evaluate the effect of sildenafil citrate on endometrial development in women with history of recurrent implantation failure after IVF. Setting: This study was conducted in obstetrics and gynecology department of Ain Shams University. Patients and methods: this is arandomized controlled trial on 80 women with previous two or more failed IVF. Women in group A (N=40) took oral sildenafil citrate at dose 25mg tab/ 6h daily from day six of induction of ovulation until day of HCG administration; while those in group B (N=40) took placebo tablets. Outcome measuers: The primary outcome was change in endometrial thickness before and after intervention. Results: Endometrial thickness in both groups was statistically insignificant between the two groups when measured in day 6 with p-value 0.070.Endometrial thickness on day of HMG injection measured and found that it was higher in group A(Sildenafil Group) than group B(Placebo Group) with significantly increased statistically difference between the two groups with p-value <0.001. Conclusion: sildenafil citrate leads to smooth muscle relaxation and vasodilation. This may enhance endometrial development and increased pregnancy rate in females undergoing IVF which may be attributed to the increase in the endometrial thickness.

Characteristics of peripheral blood NK and NKT-like cells in euthyroid and subclinical hypothyroid women with thyroid autoimmunity experiencing reproductive failure

Thyroid autoimmunity (TAI) appears to play a crucial role in female infertility, recurrent pregnancy loss and IVF failure. Thyroid autoantibodies against thyroid peroxidase and thyroglobulin have been shown to represent an independent risk factor for infertility and miscarriage. Moreover, thyroxin hormone administration reduces the risk of obstetrical complications in TAI positive women.The aim of our present study was to investigate the immunological background of female infertility and recurrent pregnancy loss in euthyroid and subclinical hypothyroid women with TAI focusing on innate immunity.Phenotypic and functional analysis was carried out on peripheral blood mononuclear cells from healthy donors and TAI patients by flow cytometry. Our findings show Th1 oriented changes of innate immunity in the peripheral blood of women suffering from thyroid autoimmunity. Elevated NK and NKT-like cells ratios and enhanced natural cytotoxicity of TAI positive women reveal an altered immune status with possible negative impact on pregnancy outcome. It is important to notice that immune alterations are already established in the euthyroid phase of autoimmune thyroiditis before endocrine dysfunction develops and only the presence of thyroid autoantibodies indicate TAI condition.For this reason, screening of healthy women of reproductive age for the presence of thyroid autoantibodies would be beneficial not only from the endocrinological aspect but from the reproductive point of view since, although yet unexplained, thyroid hormone administration may improve pregnancy outcome.

Leveraging artificial intelligence for more data-driven patient counseling after failed IVF cycles

Baseline metrics such as age and hormone levels are used to counsel patients undergoing IVF. For patients who fail multiple cycles, counseling can become more challenging and cycle-level metrics become an important consideration. As datasets grow, artificial intelligence (AI) systems are augmenting the diagnostic and prognostic capabilities of the human brain. The limitation is that these systems are only as smart as the input data they are trained on. However, the advantage is that they are unbiased, bring greater standardization to counseling, and often yield non-obvious insights.

The effect of endometrial injury on implantation and clinical pregnancy rates

Aim: To assess the effect of endometrial scratching (ES) on in vitro fertilization-embryo transfer outcome (IVF-ET)Materials and methods: Retrospective matched case control study including all fresh IVF cycles performed between January 2006 and December 2012 at an academic IVF center. ES with an endometrial biopsy catheter was performed in the cycle preceding the index IVF cycle. Patients (n = 238) were pair matched with controls according to age, number of previous failed IVF cycles and number of embryos transferred.Results: Demographic and cycle characteristics were comparable in all of the following: age, number of previous cycles, number of collected oocyte, number of embryos transferred and quality of transferred embryos. Implantation, clinical and ongoing pregnancy rates were comparable in both groups (28%, 34% and 18.4% vs 30%, 40.3% and 29%, in ES group and controls, respectively). Logistic regression analysis found no significant association between ES and pregnancy rate.Conclusions: Mechanical endometrial stimulation did not improve implantation and pregnancy rates. Furthermore, no factors that may predict which patients could benefit from ES were identified. Further prospective studies are warranted to evaluate possible benefits in different subsets of patients such as patients with recurrent implantation failures.

The effect of endometrial scratch on natural-cycle cryopreserved embryo transfer outcomes: a randomized controlled study

The benefit of endometrial scratch (ES) prior to embryo transfer is controversial. Systemic analysis has confirmed its potential benefit, especially in women with repeated IVF failures, yet most studies have focused on fresh embryo transfer, and its effect on vitrified-warmed embryo transfer (FET) cycles is yet to be explored. We hereby present our prospective, double-blind, randomized controlled study on the evaluation of the implantation and pregnancy rate after ES prior to natural-cycle FET. A total of 299 patients underwent natural-cycle FET and were randomized to receive ES (n = 115) or endocervical manipulation as control (n = 114) prior to FET cycle, and a total of 196 patients had embryo transfer (93 patients in each group). Our study showed no significant difference in the implantation and pregnancy rate, as well as the clinical and ongoing pregnancy or live birth rates between the two groups. It appears that ES does not have any beneficial effect on an unselected group of women undergoing FET in natural cycles. Further studies on its effect in women with recurrent implantation failure after IVF are warranted.