Pregnancy Rates In IVF Cycles Research Articles

Does the etiology of thin endometrium impact on pregnancy rates in IVF cycles?

Does the etiology of thin endometrium impact on pregnancy rates in IVF cycles?

P-538 The association between Clinical Pregnancy Rate in IVF-Cycles and Endometrial Receptivity based on a Novel Ultrasonographic Endometrial Receptivity Scoring System

Abstract Study question Our study was aimed towards determining whether Ultrasound based assessment of Endometrial features like blood flow, echopattern and thickness, can correlate with IVF pregnancy rates. Summary answer It was found that Clinical Pregnancy Rate in IVF cycles improved as the Ultrasound based Endometrial Receptivity Score increased. What is known already Establishing a successful pregnancy depends on the endometrium and embryo. Suboptimal endometrial receptivity account for one-third of implantation failures. Despite the in-depth understanding of the processes associated with embryo-endometrial crosstalk, little progress has been achieved for diagnosis and treatments for suboptimal endometrial receptivity. Continuously mature embryo laboratory operation technology and embryo culture technology have significantly improved the quality of embryos. In addition, because of its accuracy and non-invasiveness, transvaginal ultrasound is widely used in the field of assisted reproduction, not only for monitoring follicles, but also for evaluating endometrial receptivity and this technique can help in achieving improved pregnancy rates. Study design, size, duration This was a prospective study carried out from 2020 to 2022 in which 275 participants were recruited. Exclusion Criteria were the following: congenital uterine anomalies or acquired uterine diseases, submucosal myoma, intrauterine adhesion, uterine effusion and adenomyosis, hydrosalpinx; endometriosis; pre-implantation genetic test cycles, freeze-thaw embryo transfer cycles which all transferred embryos were non-high quality embryos. That is to say, FET cycles with the transfer of at least one high-quality embryo were included in the analysis. . Participants/materials, setting, methods 275 patients underfoing FET cycle were included in this prospective study carried out from January 2020 to December 2022. Endometrial preparation protocols included natural ovulatory cycles, ovulation induction cycles, and hormone replacement treatment cycles. Transvaginal ultrasound monitoring of endometrial thickness and the diameter of the dominant follicle began on the 10-12th day of menstrual cycle. Embryo transfer was timed accordingly and frozen embryo transfer carried out. Main results and the role of chance A total number of 275 patients of FET were analyzed. It was found that only the echo of the endometrial central line was different between the pregnant group and non-pregnant group. Other parameters, such as endometrial thickness, volume, endometrial peristalsis, or the endometrial blood flow were not statistically different between the two groups. Then, according to the relationship between the different groups and the clinical pregnancy rate, a score of 0 to 2 was respectively scored. The sum of the scores for the six items was the patient’s endometrial receptivity score. It showed that the clinical pregnancy rate increased as the endometrial receptivity score increased, and when the receptivity score reaches at least 5, the clinical pregnancy rate is significantly improved (58.2% versus 40.4%, P = 0.001). The echogenicity of the endometrial functional layer in the pregnancy group was more homogeneous, but it did not reach statistical significance. Other parameters, such as endometrial thickness, volume, the presence or absence of endometrial peristalsis, the direction of endometrial peristalsis, or the endometrial blood flow were not statistically different between the two groups. Limitations, reasons for caution In the absence of data of live birth rate, we considered clinical pregnancy rate as a proxy outcome to confirm receptive endometrium. Moreover, the sample size of the study was relatively small, and it is necessary to further expand the sample size to verify our conclusions. Wider implications of the findings We developed an endometrial receptivity scoring system and demonstrated its validity. It may aid clinicians in choosing the useful marker in clinical practice and for informing further research. As Ultrasonography is a simple and non-invasive diagnostic tool, the cost of the IVF cycle will also reduce. Trial registration number NOT REQUIRED

Transfer mosaic embryos has similar outcomes in pregnancy rates in IVF cycles compared euploid embryos

Background and Aim: There is evidence that blastocysts classified as mosaics as a result of preimplantation genetic testing for aneuploidy (PGT-A) by next-generation sequencing (NGS) less likely to implant and miscarry more often than euploid embryos, but such embryos still be able to produce chromosomally normal and viable pregnancies. Different genetic communities recommend using mosaics for transfer only when no euploid embryos are available. Genetic counseling is necessary before the transfer of a mosaic embryo is considered.

Pregnancy rate in IVF patients with unexpected poor response to ovarian stimulation

Objective To evaluate whether an unexpected poor response (cases with ≤3 oocytes) leads to a reduction in the pregnancy rate in IVF cycles compared to a suboptimal response (controls with 4-9 oocytes) in women with adequate ovarian reserve. Methods A nested case-control study performed in a retrospective cohort of couples undergoing IVF at the Infertility Unit of the ASST Lariana. Cases and controls had adequate ovarian reserve and were matched 1:1 for female age and number of previous cycles. Cumulative clinical pregnancy rate per oocyte retrieval was the main outcome. Results Overall, 113 cases and 113 matched controls were included; the median number of available oocytes was 2 and 6, respectively. The cumulative pregnancy rate per cycle was significantly reduced in cases compared to controls with a crude odds ratio = 0.45 [95% Confidence Interval: 0.28-0.82]. A binomial logistic model indicated that an increase in one oocyte increases the odds for cumulative pregnancy rate per cycle by 1.27 in women with 9 oocytes or less. The cumulative pregnancy rates per cycle in cases and controls, according to female age were respectively: 29% versus 54% in patients aged <35 years (p = 0.036); 22% versus 43% in patients aged 36-39 years (p = 0.048) and 11% versus 13% in patients 40-45 years old (p = 0.72). Patients belonging to older age groups showed decreasing probability of cumulative clinical pregnancy rates both among cases and controls group (p < 0.05). Conclusions The number of available oocytes significantly affects the probability of success in IVF cycles with unexpected impaired ovarian response.

The effect of hyaluronic acid in embryo transfer media in donor oocyte cycles and autologous oocyte cycles: a systematic review and meta-analysis.

Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles? The best available evidence indicates that the addition of HA to embryo transfer medium is clinically beneficial in cycles with autologous oocytes. There is a known clinical benefit of HA addition to embryo transfer media but it is not known if HA affects donor and autologous oocyte cycles differently. A systematic review with meta-analysis was performed. The Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL via Cochrane Register of Studies Online (CRSO), MEDLINE, Embase and PsycINFO electronic databases (until 8 January 2020) were searched for randomized controlled trials (RCTs) examining the effect of HA in embryo transfer medium on pregnancy outcomes. RCTs with separate donor and autologous oocyte data that compared embryo transfer medium with functional HA concentrations (0.5 mg/ml) to those containing no or low HA concentrations (0.125 mg/ml) were included. Two review authors independently selected trials for inclusion, extracted data and assessed the included studies using the Cochrane risk of bias assessment tool. Pooled risk ratios and 95% CIs were calculated. A summary of findings table was generated using Grading of Recommendations, Assessment, Development and Evaluation criteria. Judgements about evidence quality were justified and incorporated into the reported results for each outcome. Fifteen studies, totalling 4686 participants, were analysed. In autologous oocyte cycles, live birth increased from 32% to 39% when embryo transfer media contained functional HA concentrations (risk ratio (RR) 1.22, 95% CI 1.11-1.34; nine studies, 3215 participants, I2 = 39%, moderate-quality evidence (number needed to treat (NNT) 14). HA-enriched media increased clinical pregnancy and multiple pregnancy rates by 5% and 8%, respectively (RR 1.11, 95% CI 1.04-1.18; 13 studies, 4014 participants, I2 = 0%, moderate-quality evidence, NNT 21) and (RR 1.49, 95% CI 1.27-1.76; 5 studies, 2400 participants, I2 = 21%, moderate-quality evidence, number needed to harm 13). Conversely, in donor oocyte cycles, HA addition showed little effect on live birth and clinical pregnancy (RR 1.12 95% CI 0.86-1.44; two studies, 317 participants, I2 = 50%, low-quality evidence) and (RR 1.06, 95% CI 0.97-1.28; three studies, 351 participants, I2 = 23%, low-quality evidence). There was insufficient available information on multiple pregnancy in donor oocyte cycles and on total adverse effects in both groups to draw conclusions. There were limited studies with separate data on donor oocyte cycles and limited information on oocyte quality. Additionally, one-third of the included studies did not include the main outcome, live birth rate. There is a moderate level of evidence to suggest that functional HA concentration in embryo transfer medium increases clinical pregnancy, live birth and multiple pregnancy rates in IVF cycles using autologous oocytes. This effect was not seen in donor oocyte cycles, indicating either intrinsic differences between donor and autologous oocytes or lack of statistical power. The combination of HA addition to transfer media in cycles using autologous oocytes and a single embryo transfer policy might yield the best combination, with higher clinical pregnancy and live birth rates without increasing the chance of multiple pregnancies. No financial assistance was received. The authors have no competing interests. N/A.

Towards an Improved Understanding of the Effects of Elevated Progesterone Levels on Human Endometrial Receptivity and Oocyte/Embryo Quality during Assisted Reproductive Technologies.

Ovarian stimulation is an indispensable part of IVF and is employed to produce multiple ovarian follicles. In women who undergo ovarian stimulation with gonadotropins, supraphysiological levels of estradiol, as well as a premature rise in progesterone levels, can be seen on the day of hCG administration. These alterations in hormone levels are associated with reduced embryo implantation and pregnancy rates in IVF cycles with a fresh embryo transfer. This article aims to improve the reader’s understanding of the effects of elevated progesterone levels on human endometrial receptivity and oocyte/embryo quality. Based on current clinical data, it appears that the premature rise in progesterone levels exerts minimal or no effects on oocyte/embryo quality, while advancing the histological development of the secretory endometrium and displacing the window of implantation. These clinical findings strongly suggest that reduced implantation and pregnancy rates are the result of a negatively affected endometrium rather than poor oocyte/embryo quality. Understanding the potential negative impact of elevated progesterone levels on the endometrium is crucial to improving implantation rates following a fresh embryo transfer. Clinical studies conducted over the past three decades, many of which have been reviewed here, have greatly advanced our knowledge in this important area.

P–315 Ultrasound diagnosis of adenomyosis: impact on pregnancy rate in ivf cycles with donated oocytes

Abstract Study question The aim was to evaluate in patients who underwent embryo transfer (ET) in an oocyte donation cycle, the impact of adenomyosis, diagnosed by transvaginal sonographic (TVS), on the implantation rate. Summary answer We observed a slightly higher miscarriage rate in the first trimester in patients with adenomyosis in particular in the diffuse type. What is known already What we know from literature is that there are pro studies such as Costello and Vercellini’s which show a reduced pregnancy rate and birth rate, and cons studies which find no effects at all of adenomyosis on IVF treatments. However, both show an increased risk of miscarriage and obstetric complications Study design, size, duration This prospective observational study involved a total of 72 patients: 33 with adenomyosis and 39 without adenomyosis from June 2019 to December 2020. All had a workup which included history, pelvic exam and 2/3D TVS scan which was saved as images, videoclips and volumes and stored. The off line evaluation was performed blind to IVF indication and outcomes by expert sonographer, who assessed the presence or absence of TVS signs of adenomyosis. Participants/materials, setting, methods All the patients aged ≤ 45 years old undergoing, for several personal problems, their first oocyte donation at IVI center Rome.Patients were divided into 2 groups according to findings on a baseline pre-treatment TVS: patients with and without adenomyosis. In the patients with adenomyosis, the disease was further classified according to type (diffuse,focal), localization (inner and outer myometrium) and extension inside the uterus (mild, moderate, severe) and correlated to pregnancy rate and outcome Main results and the role of chance A total of 72 patients were included in this study: 33 with adenomyosis and 39 without adenomyosis. The presence, type and degree of adenomyosis doesn’t show a correlation to embryo implantation rate (64.1% in the control group vs 63.6% in adenomyosis group). However we found an increased risk of early miscarriage in the patients with adenomyosis ( 12% in the control group vs 23.8% in adenomyosis group). Women with adenomyosis that infiltrated only the external myometrium showed a lower pregnancy rate (40%) compared to those who had the involvement of only the inner myometrium (77,7%). The presence of ultrasound findings of focal disease was associated with a lower pregnancy rate (53,3%) compared to the diffuse disease (72,2%); We observed a slightly higher miscarriage rate in the first trimester in patients with adenomyosis in particular in the diffuse type .The presence, type and degree of adenomyosis doesn’t show a correlation to embryo implantation rate. Limitations, reasons for caution Most of the patients included in our study has an age &amp;gt; 40. This could determine an increased number of high-risk pregnancies. Wider implications of the findings: Results of this study may be used to evaluate the impact of different medical or surgical treatment in women with adenomyosis undergoing IVF. Trial registration number Not applicable

P–498 Patient’s pregnancy rates after IVF fresh embryo transfer positively correlates to the number of visual connections to live blastocyst development images of own embryos

Abstract Study question Looking at time-lapse images of own embryos during the five days of culture, as a patient’s active behaviour, may help to increase pregnancy rates? Summary answer The number of visual connections to live blastocyst development images of own embryos positively correlates to patient’s pregnancy rates after fresh single blastocyst transfer. What is known already In human reproduction, despite the evidence that infertility itself and reproductive treatments can produce anxiety and stress, the impact of emotions on pregnancy outcomes is unknown and probably underestimated. The interaction between psyche, nervous, immune and endocrine systems (PNIE) is well known and has been applied to understand and treat different pathological conditions. Patient’s active behaviour during IVF treatments appears to be a positive strategy to decrease women’s anxiety and stress, thus to increase fertility quality of life and pregnancy outcomes. Study design, size, duration Retrospective comparative study of 934 patients undergoing fresh IVF cycles during three years. To avoid any bias related to oocyte and embryo factors, we only included egg donation cycles in the study, and ≥3BB (Gardner score) single embryo transfers. All embryo cultures were performed in time-lapse incubator and patients could connect on-line to their embryo’s images before single blastocyst transfer. We evaluated the impact of visual connections to live embryo images on pregnancy rates. Participants/materials, setting, methods On day one of embryo culture, consenting patients received an individualized and secure link allowing them to connect on-line to images of their own embryos any time during the five days of culture. Patients were divided in five groups depending on the number of on-line visualisations (A = 0; B = 1–10; C = 11–20; D = 21–30; E &amp;gt; 30). Pregnancy and clinical pregnancy rates were compared between the five groups. Chi-square test for a large contingency table was performed to compare all groups Main results and the role of chance The distribution of patients in the five groups, based on number of visualizations, resulted as follows: 287 in group A; 328 in group B; 156 in group C; 80 in group D; 83 in group E. The five groups were homogeneous and there were no statistically significant differences in recipient’s ages (A 42.8±3.9 years; B 41.9±3.9 years; C 41.8±4.5 years; D 42.8±4.1 years; E 41.9±4.4 years) and in donor’s ages (A 25.5±4.3 years; B 26.9±4.4 years; C 27.1±4.2 years; D 26.4±4.5 years; E 26.5±4.1 years) among the five groups. We observed a progressive positive trend between the number of on-line visualisations and pregnancy rates, reaching statistical significance for group E (&amp;gt;30 visualizations) compared to the others groups. In group E, pregnancy rates and clinical pregnancy rates per fresh single blastocyst transfer were respectively 72.3% and 65.1%, significantly higher when compared to the others groups (p &amp;lt; 0.01, p &amp;lt; 0.001): group A 61% and 50.9%, group B 63.1% and 56.1%, group C 64.1% and 55.1%, group D 65% and 53.8%. Limitations, reasons for caution Time-lapse incubator is needed as well as a strong informatics setting to ensure secure and personalised on-line connection to each patient at any time during the five days of culture. Endocrine and endometrial biomarkers should be proposed and evaluated in further clinical trials to better understand these results. Wider implications of the findings: Repeated on-line visualization of own embryos images before fresh blastocyst transfer enhances pregnancy rates in IVF cycles. We propose that repeated visual stimuli of images produces a positive emotional connection between patients and their own developing embryos, thus reducing anxiety and enhancing recipient’s endometrial receptivity. Trial registration number Not applicable

LOW EUPLOIDY RATE DOES NOT AFFECT CLINICAL OUTCOMES IN IVF PGT CYCLES WITH SINGLE EMBRYO TRANSFER (SET) - A 2391 SETS REVIEW

Recent publications have demonstrated significant improvement in IVF treatment outcomes by implementing NGS/SNP-based preimplantation genetic testing (PGT) while transferring fewer embryos. Euploidy rates can vary significantly even for the same patient from cycle to cycle. The objective of this study was to evaluate clinical pregnancy rates in IVF cycles with low euploidy rates. A retrospective study of IVF PGT outcome data from blastocysts biopsied on day 5 or day 6 was conducted to identify differences in clinical pregnancy rates. 1646 cycles (13869 embryos, 6.2 ± 3.81 per cycle) of IVF PGT treatment where at least one euploid embryo was available between January 2013 and January 2020 were included in the study. 2391 single embryo transfers (SET) were performed (average maternal age – 36.2 ± 4.7). All SETs were divided in 4 groups based on euploidy rates: 1-25% (192 SETs), 26-50% (819 SETs), 51-75% (774 SETs), and 75-100% (606 SETs). All embryos were vitrified after biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. Clinical pregnancy rate (PR) was defined by the presence of a fetal heartbeat at 6 - 7 weeks of pregnancy. Analysis of the data showed no statistically significant difference in clinical pregnancy rates between the group with lowest (1-25%) and the group with highest euploidy rates (76-100%): 65.63% (126/192) vs 65.18% (395/606), respectively, χ2 = 0.013, OR = 1.02, CI = 0.725 – 1.435, p<0.05. Even in the group of patients with 100% euploidy rate (average age 34.4 ± 4.9) the clinical pregnancy rate was not statistically different – 63.5% (233/367, p<0.05). For some patients low euploidy rates were manifested also in a small number of euploid embryos available for transfer – 29.7% (489/1646) of patients in our study had only one euploid embryo. At the same time, no statistically significant difference was found in the clinical pregnancy rates in the cycles where only one euploid embryo was available versus IVF PGT cycles where four or more euploid embryos were available for a transfer: 65.24% (319/489) vs 66.96% (675/1008), respectively, χ2 = 0.507, OR = 0.926, CI = 0.737 – 1.162, p<0.05. Analysis of the data proved that low euploidy rate does not affect clinical outcomes in IVF PGT cycles with single embryo transfer. Single embryo transfer should be imperative in PGT cycles regardless of the euploidy rate or the total number of euploid embryos available for transfer.

VITAMIN D3 (25 OH D) LEVELS IN FOLLICULAR FLUID STRONGLY CORRELATE WITH DEVELOPMENTAL POTENTIAL AND GRADES OF EMBRYO IN IVF CYCLES

To evaluate if follicular-fluid (FF) levels of Vitamin D3 correlate with the oocyte and embryo developmental competence. Prospective study of reproductive age women (n=300, 22-42 years) undergoing IVF without any previous history of vitamin D3 supplementation. On day of oocyte pickup (OPU), fluid from first aspirate of each follicle was pooled for each patient and centrifuged to obtain clear follicular fluid. Vitamin D3 levels were measured in FF using RIA diagnostic kits. Sequential culture to blastocyst stage was done and blastocysts were graded as top, good and poor quality as per standard evaluation criteria. All blastocysts were vitrified for transfer in next natural cycle. All women underwent controlled ovarian hyper-stimulation (COH) with recombinant FSH. Women with endometriosis, tuberculosis, hydrosalpynx, poor ovarian response (≤ 3 retrieved oocytes) to COH and male partners with severe or moderate male factor were excluded from the study. Cycles were classified into Low (< 41 ng/ml; n=152) and High (> 41 ng/ml; n=148) FF Vitamin D3 groups on the basis of their median values. Rates of fertilization, cleavage, blastocyst formation and grades of blastocysts formed were recorded in both the study groups. There was no significant difference in age, number of eggs retrieved and mean MII oocytes (p>0.05) between the two study groups. However, rates of fertilization (93.3 ± 22.6 vs. 86.1 ± 29.5% P: 0.0205) and cleavage (87.0±18.5 vs. 79.3±24.6% p:0.02) were significantly higher in low group than in high FF Vitamin D3 group. Interestingly, although overall Blastocyst formation rate remained comparable (50.3 ±37.9 vs. 54.1 ± 35.4% : P value 0.3740); the percentage of top (34.4 ±0.4 vs 24.2 ±0.8%, P= 0.0183) and good 37.8 ± 0.69 vs 21.4 ± 0.72%, p= 0.0002) grade blastocysts were significantly higher in low FF Vitamin D3 group than in high FF Vitamin D3 group. Importantly, poor quality blastocysts were significantly high in high FF Vitamin. D3 compared to Low FF Vit. D3 group (45.0 ± 38.5 vs 26.3 ± 33.0 %, P value: < 0.0001). FF Vit. D3 correlated with top grade blastocysts (Pearson r= 0.56). There have been contradictory results of correlation between serum levels of Vitamin D3 and embryo quality. However, since follicular-fluid is the microenvironment which reflects the fate of follicle and oocyte development, study of this correlationship in FF, as done in our study, seems more logical. Also, with changes in weather conditions and carbon emission affecting the ozone layer all over the world, the natural synthesis of Vitamin D3 seems to be disturbed. Therefore, it is extremely prudent to evaluate this hormone to improve embryo development and pregnancy rates in IVF cycles. FF level of Vitamin D3 is potentially predictive of embryo quality and facilitates non-invasive selection of best blastocyst for transfer.

Progesterone in Assisted Reproduction: Classification, Pharmacology and Its Clinical Coorelation: A Commentary

The modulating effects of progesterone on endometrium structure and function are the basis for successful outcome in reproductive treatments. Considering this, progesterone has a big role in treatment of infertility and supporting the ongoing pregnancy. In this review article we have attempted to review different forms of progesterone, their metabolism in the body and the role played by exogenous as well as endogenous progesterone in assisted reproductive technologies (ART). Elevated serum progesterone levels at the end of the follicular phase in controlled ovarian stimulation (COS) leads to a poorer ongoing pregnancy rate in IVF cycles due to reduced endometrial receptivity.

DOES PROBIOTIC AND PREBIOTIC TREATEMENT IN IVF CYCLES OF INFERTILE WOMEN WITH INTESTINAL DYSBIOSIS, AFFECT PREGNANCY RATE?

Background: Several findings show how as the intestinal microbiota regulates some important metabolic and physiological body functions, as production of toxic or useful substances, induction of inflammatory processes and interaction with immune system. Alterations of the intestinal microbiota can occur by changes in composition (dysbiosis), function, or microbiota-host interactions and they can be directly correlated with several diseases as bacterial vaginosis (BV). Objectives: the aim of this study is to understand if there is a correlation between acute intestinal dysbiosis condition and the failure in IVF freeze embryo transfer(FET)cycles, and if a prebiotic and probiotic treatment can improve the success rate. Search strategy: we investigate about the incidence of pregnancy rate in acute-severe dysbiotic patients and prebiotics–probiotics treated patients undergoing to a FET cycle. Selection criteria: 53 patient with acute or severe intestinal dysbiosis undergoing IVF cycle was recruited and randomized in two group. Group A (n=29) (control group) and Group B (n=24) have to transfer two freeze embryos each. Group B was treated with prebiotic and probiotic for at least two months to reduce the dysbiosis condition from acute-severe to mild-moderate level. Main results: After FET in the group A there have been 5 ongoing pregnancy and 3 born baby, in the group B (treated group) there was been 15 pregnancy(p&lt;0,05) and 12 born baby (p&lt;0,05) Conclusion: Our result show that a treatment whit probiotic and prebiotic is able to increase pregnancy rate in IVF cycles of infertile women affected by acute or severe intestinal dysbiosis, by modulation of some crucial mechanisms involved in embryo implantation.

Mosaic segmental aneuploidy in trophoectoderm does not affect pregnancy rates in IVF cycles

Mosaic segmental aneuploidy in trophoectoderm does not affect pregnancy rates in IVF cycles

Association between ambient air pollution and pregnancy rate in women who underwent IVF.

Are the concentrations of five criteria air pollutants associated with probabilities of biochemical pregnancy loss and intrauterine pregnancy in women? Increased concentrations of ambient particulate matter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO) during controlled ovarian stimulation (COS) and after embryo transfer were associated with a decreased probability of intrauterine pregnancy. Exposure to high ambient air pollution was suggested to be associated with low fertility and high early pregnancy loss in women. Using a retrospective cohort study design, we analysed 6621 cycles of 4581 patients who underwent one or more fresh IVF cycles at a fertility centre from January 2006 to December 2014, and lived in Seoul at the time of IVF treatment. To estimate patients' individual exposure to air pollution, we computed averages of hourly concentrations of five air pollutants including PM10, NO2, CO, sulphur dioxide (SO2) and ozone (O3) measured at 40 regulatory monitoring sites in Seoul for each of the four exposure periods: period 1 (start of COS to oocyte retrieval), period 2 (oocyte retrieval to embryo transfer), period 3 (embryo transfer to hCG test), and period 4 (start of COS to hCG test). Hazard ratios (HRs) from the time-varying Cox-proportional hazards model were used to estimate probabilities of biochemical pregnancy loss and intrauterine pregnancy for an interquartile range (IQR) increase in each air pollutant concentration during each period, after adjusting for individual characteristics. We tested the robustness of the result using generalised linear mixed model, accounting for within-woman correlation. Mean age of the women was 35 years. Average BMI was 20.9 kg/m2 and the study population underwent 1.4 IVF cycles on average. Cumulative pregnancy rate in multiple IVF cycles was 51.3% per person. Survival analysis showed that air pollution during periods 1 and 3 was generally associated with IVF outcomes. Increased NO2 (adjusted HR = 0.93, 95% CI: 0.87, 0.99) and CO (0.94, 95% CI: 0.89, 1.00) during period 1 were associated with decreased probability of intrauterine pregnancy. PM10 (0.92, 95% CI: 0.85, 0.99), NO2 (0.93, 95% CI = 0.86, 1.00) and CO (0.93, 95% CI: 0.87, 1.00) levels during period 3 were also inversely associated with intrauterine pregnancy. Both PM10 (1.17, 95% CI: 1.04 1.33) and NO2 (1.18, 95% CI: 1.03, 1.34) during period 3 showed positive associations with biochemical pregnancy loss. The district-specific ambient air pollution treated as an individual exposure may not represent the actual level of each woman's exposure to air pollution. Smoking, working status, parity or gravidity of women, and semen analysis data were not included in the analysis. This study provided evidence of an association between increased ambient concentrations of PM10, NO2 and CO and reduced probabilities for achieving intrauterine pregnancy using multiple IVF cycle data. Specifically, our results indicated that lower intrauterine pregnancy rates in IVF cycles may be linked to ambient air pollution during COS and the post-transfer period. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013 R1A6A3A04059017, 2016 R1D1A1B03933410 and 2018 R1A2B6004608) and the National Cancer Center of Korea (NCC-1810220-01). The authors report no conflicts of interest. N/A.

IVF Sikluslarında Oosit Sayısının Gebelik Oranlarına Etkisi

IVF Sikluslarında Oosit Sayısının Gebelik Oranlarına Etkisi

Estradiol use in the luteal phase and its effects on pregnancy rates in IVF cycles with GnRH antagonist: a systematic review.

For all the steps of in vitro fertilization to occur successfully, factors such as the quality of retrieved oocytes and endometrial receptivity to the embryo must be ensured. Current studies have shown that endometrial receptivity can be optimized using dedicated exogenous progesterone for luteal phase support in assisted reproduction cycles. But it has not yet been established the benefits of additional use of estradiol in this support. Analyzing pituitary suppression protocols that employ GnRH antagonists, this review will address literature publications between the years 2000-2016, shedding light on this issue to answer questions about the benefits of supplementation.

Влияние разных протоколов овариальной стимуляции на эмбриологические характеристики и эффективность программ вспомогательных репродуктивных технологий

There are controversial data about the effect of different controlled ovarian hyperstimulation (COS) protocols on embryological stage and in vitro fertilization (ivf) outcomes. The aim of our study was to evaluate embryological and clinical outcomes according to COS protocol.Material and methods. This prospective cohort study included 521 patients treated with ivf. The patients were divided into the following 5 groups: group 1 - women treated with gonadotrophin-releasing hormone (GnRH) antagonists: subgroup 1a (n=143) - triggering of final oocyte maturation with human chorionic gonadotropin, subgroup 1b (n=85) - with GnRH agonist. Group 2 (n=119) - women treated with GnRH agonists, group 3 (n=82) - women treated in «modified» natural cycle, group 4 (n=92) - women treated with GnRH antagonists and corifollitropin alfa.Results. The lowest percent of empty follicles (78.9%) was observed in group 2. The proportion of mature oocytes (number of mature oocytes|number of cumulus-oocyte complexes) was highest in groups 1a and 2 in comparison with groups 1b and 4 (87.9 and 87.2% vs. 84.0 and 81.9%, respectively). The fertilization rate was maximal in group of women with «modified» natural cycle. The proportion of embryos with different morphological quality was similar in the groups. A clinical pregnancy was observed in 48 (33.6%) cases in group 1a, in 26 (30.6%) patients in group 1b, in 39 (32.8%) casesin group 2 in 7 (8.5%) cases in group 3 and in 17 (18.5%) cases in group 4 (p<0.0001).Conclusions. The selection of COS protocol has an impact on parameters of folliculo-, oogenesis and embryogenesis, as well as on clinical pregnancy rate in ivf cycles. The clinical pregnancy rate also depends on baseline characteristics of women.

Strategies for Poor Responders in IVF Cycles

The desired objective of controlled ovarian stimulation (COS) is to allow the growth of a cohort of follicles and to facilitate the recovery of a large number of fertilizable oocytes. However, poor responders with low ovarian reserve often fail to respond adequately despite the maximal dose of gonadotropins administered, with the results that the number as well as quality of oocytes harvested may be very low. These results lead to a significant decrease of pregnancy rate in IVF cycles. Therefore, successful COS for poor responders continues to be a major challenge in IVF program. In this review, I will describe strategies for improvement of ovarian response to COS in poor responders. The strategies described may provide a means of augmenting follicular recruitment by endocrinological manipulation for poor responders undergoing IVF.

The 112.5IU r-hFSH starting dose is enough for successful IVF in AMH ≥3 ng/ml

Controlled ovarian hyperstimulation(COH) is needed in order to improve the pregnancy rate in IVF cycles. Recently, there has been an interest in using a much lower dosage of FSH for mild stimulation in IVF protocols. The purpose of this study was to assess the mild stimulation with starting dose of recombinant human FSH (r-hFSH) 112.5IU could be enough for successful IVF outcomes in patients with AMH ≥3ng/ml in IVF cycles. Retrospective. We retrospectively reviewed 657 consecutive cycles of 594 normo-ovulatroy women(AMH ≥3ng/ml) who underwent IVF treatment over a 3-year period (2010 –2012) at our institution. Our study population was divided into two groups according to r-hFSH starting dose for COH-IVF cycles. Group A: r-hFSH(Gonal-F®) starting dose 112.5IU (n=257), Group B: starting dose 150IU (n=400) in women with AMH ≥3ng/ml. Outcomes were compared the number of oocytes retrieved, total dose of r-hFSH, total r-hFSH stimulation days, clinical pregnancy and abortion rate between the two groups.. The total dose of r-hFSH administered was significantly different between the group A and the group B (1055.1 IU and 1365.5 IU, p<0.01). The total number of r-hFSH administration days (9.6days (5–17) and 9.1days (9–16), p=0.08) and embryo quality were comparable in both groups. Although the number of retrieved oocytes (14.9 ± 6.8 vs. 13.3 ± 6.1, P<0.01) and fertilized oocytes(9.1 ± 4.9 vs. 8.8 ± 4.3, P=0.02) were significantly higher in group A than group B. However, the pregnancy rate (63.4% vs 58.3%, p=0.139) and abortion rate (12.9% vs13.3%) were not significantly different between both groups. In our results, a total mean r-hFSH dose of 1055.1IU with the 112.5IU starting dose in COH cycle was sufficient for the number of retrieved oocytes and the pregnancy rates in patients with AMH≥3ng/ml. Therefore, These seems clear that a subset of patients with AMH ≥3ng/ml undergoing ovarian stimulation can be adequately treated with a 112.5 IU starting dose of r-hFSH.

Estradiol on the second day is not related to pregnancy rate

The real importance of estradiol levels on the second day of the menstrual cycle in IVF results remains controversial. Up to now, there are few studies in the literature and there is no consensus among the authors if high level of estradiol on the beginning of the cycle reduces the chances of pregnancy. The importance to know if this relationship exist is in fact, is to analyze the possibility to start or cancel an IVF cycle when estradiol is above 75 ng / mL. This study aims to assess if the levels of serum estradiol on the second day of the menstrual cycle is related with pregnancy rates in IVF cycles.