Higher Clinical Pregnancy Rate Research Articles

Preconception Evaluation Before In Vitro Fertilization.

Infertility poses a substantial public health problem for women of reproductive age, in the United States and globally. Infertility can be overcome with a variety of emerging assisted reproductive technologies (ARTs). In vitro fertilization (IVF) currently represents the most commonly utilized method of ART and is typically associated with the highest clinical pregnancy rate and live birth rate compared with other infertility treatment options. However, proper preconception evaluation and counseling is paramount for optimizing IVF and pregnancy outcomes. This article aims to outline current guidelines and recommendations for comprehensive preconception evaluation before initiation of IVF. Articles were obtained from PubMed, ACOG committee opinions 781 and 762, and relevant textbook chapters. A variety of recommendations and best practices exist for optimally managing patients seeking IVF. Special attention must be paid to the workup of certain patient populations, such as those with age older than 35 years, uterine abnormalities, comorbidities (especially hypertension, diabetes, and thrombophilias), and obesity. In addition, many lifestyle factors must be addressed before IVF initiation, such as smoking, illicit drug use, and inadequate nutrition. Preconception counseling and expectation management is key to optimizing pregnancy outcome. A myriad of patient and environmental factors impact the potential success rates of IVF in treating infertility. Providers must be equipped to provide data-driven, patient-centered counseling before initiation of IVF.

Modified natural protocol seems superior to natural and artificial protocols for preparing the endometrium in frozen embryo transfer cycles.

Although several studies claim higher success rates in natural cycle (NC) and modified natural cycle (mNC) protocols, currently, there is no consensus on the most effective method of endometrium preparation prior to frozen embryo transfer (FET) cycles. We aimed to find out the best protocol by comparing three different protocols for preparing the endometrium in FET cycles. This retrospective cohort study was conducted at a private in-vitro fertilization (IVF) center. Medical records of all patients enrolled in frozen embryo transfer cycles between November 2017 and February 2019 were reviewed. Group I (N.=94) included patients who underwent artificial endometrial preparation (AC), group II (N.=23) confined patients enrolled in mNC and group III (N.=12) included patients who had NC protocol. Main outcome parameters were clinical pregnancy rates, implantation rates and miscarriage rates. There was a tendency towards higher clinical pregnancy rate in mNC group. Clinical pregnancy rates of the three groups were 54.3%, 65.2% and 33.3% respectively (P=0.199). Implantation rate was significantly higher in group II (34%, 50% and 12% respectively, P=0.006). Miscarriage rates were similar for the three groups. Although not reaching a statistically significant level, there is a tendency towards higher implantation rate and pregnancy rate in mNC protocol compared to true NC and AC protocols.

The Feasibility of All-Blastocyst-Culture and Single Blastocyst Transfer Strategy in Elderly Women: A Retrospective Analysis.

Objective To investigate the feasibility and clinical outcome of the all-blastocyst-culture and single blastocyst transfer strategy in women aged ≥35 years. Methods A retrospective analysis of patients aged ≥35 years undergoing IVF/ICSI was performed from January 2017 to April 2019 in the reproductive center of the Second Affiliated Hospital of Wenzhou Medical University. A total of 155 cases treated with ovarian hyperstimulation by prolonged protocol and implemented single (84 cases) or double (71 cases) blastocyst transfer were collected. Then, patients were further divided into <38 yr. group and ≥38 yr. group, and the laboratory and clinical outcomes were compared between the groups. Results The double-blastocyst-transfer (DBT) group showed higher clinical pregnancy rate and multiple pregnancy rate and lower neonatal birth weight than those in the single-blastocyst-transfer (SBT) group (P < 0.05). However, there were no statistically significant differences between the groups in the embryo implantation rate, biochemical pregnancy rate, miscarriage rate, preterm delivery rate, and term birth rate. For patients < 38 yr., SBT significantly reduced the multiple pregnancy rate and increased the neonate birth weight without significant reduction in the clinical pregnancy rate. While in the ≥38 yr. group, there are no differences in pregnancy outcomes between SBT and DBT. Logistic regression analysis showed that the number of MII oocytes was positively correlated with the live birth rate (OR = 1.18) and negatively correlated with the miscarriage rate (OR = 0.844), suggesting that elderly patients with relatively normal ovarian reserve would obtain better prospect in pregnancy. The number of fetal heart beat in pregnancy was negatively correlated with the live birth rate (OR = 0.322) and positively correlated with the preterm birth rate (OR = 7.16). Conclusion The strategy of all-blastocyst-culture and single blastocyst transfer is feasible, safe, and effective for elderly patients with normal ovarian reserve, which would reduce the multiple pregnancy rate.

Stress in couples undergoing assisted reproductive technology.

To determine the associations between pre-treatment self-reported stress level, salivary cortisol levels, and clinical pregnancy outcome in couples undergoing assisted reproductive technology treatment (ART). Seventy-five couples (150 patients) undergoing ART treatment were enrolled in this study. Psychological variables were assessed using the Perceived Stress Scale, Beck Anxiety Inventory, State-Trait Anxiety Inventory, and Beck Depression Inventory. Salivary cortisol levels were obtained from each couple prior to commencing gonadotropin treatment at several times (upon waking and at 15, 30, and 60min after waking). There was no statistically significant association between the self-reported stress levels and the ART treatment outcome in couples. Women with a successful outcome after ART treatment had higher median salivary cortisol levels than women who had an unsuccessful result [24.7 (19.9-63.1) vs. 20.7 (10.4-30.4), respectively]. There was no statistically significant difference in the median salivary cortisol levels of men in relation to ART treatment outcome. Salivary cortisol levels of the couples were not correlated. Women who had higher mediansalivary cortisol levels in the pre-treatment period had a higher clinical pregnancy rate. This result suggests that moderately increased activity of the hypothalamic-pituitary-adrenal axis during ART treatment might be associated with successful conception.

CARTR Plus: the creation of an ART registry in Canada.

STUDY QUESTIONWhat is the status of fertility treatment and birth outcomes documented over the first 6 years of the Canadian Assisted Reproductive Technologies Register (CARTR) Plus registry?SUMMARY ANSWERThe CARTR Plus registry is a robust database containing comprehensive Canadian fertility treatment data to assist with providing evidence-based rationale for clinical practice change.WHAT IS KNOWN ALREADYThe rate of infertility is increasing globally and having data on fertility treatment cycles and outcomes at a population level is important for accurately documenting and effecting changes in clinical practice.STUDY DESIGN, SIZE, DURATIONThis is a descriptive manuscript of 183 739 fertility treatment cycles from 36 Canadian clinics over 6 years from the CARTR Plus registry.PARTICIPANTS/MATERIALS, SETTING, METHODSCanadian ART treatment cycles from 2013 through 2018 were included. This manuscript described trends in type of fertility treatment cycles, pregnancy rates, multiple pregnancy rates, primary transfer rates and birth outcomes.MAIN RESULTS AND THE ROLE OF CHANCEOver the 6 years of the CARTR Plus registry, the number of treatment cycles performed ranged from less than 200 to greater than 1000 per clinic. Patient age and the underlying cause of infertility were two of the most variable characteristics across clinics. Similar clinical pregnancy rates were found among IVF and frozen embryo transfer (FET) cycles with own oocytes (38.9 and 39.7% per embryo transfer cycle, respectively). Fertility treatment cycles that used donor oocytes had a higher clinical pregnancy rate among IVF cycles compared with FET cycles (54.9 and 39.8% per embryo transfer cycle, respectively). The multiple pregnancy rate was 7.4% per ongoing clinical pregnancy in 2018, which reflected a decreasing trend across the study period. Between 2013 and 2017, there were 31 811 pregnancies that had live births from all ART treatment cycles, which corresponded to a live birth rate of 21.4% per cycle start and 89.1% of these pregnancies were singleton live births. The low multiple pregnancy rate and high singleton birth rate are associated with the increase in single embryo transfers.LIMITATIONS, REASONS FOR CAUTIONThere is potential for misclassification of data, which is present in all administrative health databases.WIDER IMPLICATIONS OF THE FINDINGSThe CARTR Plus registry is a robust resource for ART data in Canada. It provides easily accessible aggregated data for Canadian fertility clinics, and it contains data that are internationally comparable.STUDY FUNDING/COMPETING INTEREST(S)There was no funding provided for this study. The authors have no competing interests to declare.

Could the Age Difference of a Single Calendar Year between Patients Undergoing IVF at 34, 35 or at 36 Years Old Affect the IVF Outcome? A Retrospective Data Analysis.

Background and Objectives: Clinicians are called to overcome age-related challenges in decision making during In Vitro Fertilization (IVF) treatment. The aim of this study was to investigate the possible impact of a single calendar year difference among patients aged 34, 35 and 36 on IVF outcomes. Materials and Methods: Medical records between 2008 and 2019 were analyzed retrospectively. The study group consisted of women diagnosed with tubal factor infertility. Sample size was divided in three categories at 34, 35 and 36 years of age. Embryo transfer including two blastocysts was performed for every patient. Comparisons were performed regarding hormonal profile, response to stimulation, quality of transferred embryos, positive hCG test and clinical pregnancy rate. Results: A total of 706 women were eligible to participate. Two-hundred and forty-eight women were 34, 226 were 35 while the remaining 232 were 36 years old. Regarding the hormonal profile, the number of accumulated oocytes and the quality of embryos transferred, no statistically significant difference was documented between the three age groups. Women aged 34 and 35 years old indicated a significantly increased positive hCG rate in comparison to women aged 36 years old (p-value = 0.009, p-value = 0.023, respectively). Women aged 34 and 35 years old presented with a higher clinical pregnancy rate in comparison to those aged 36 years old (p-value = 0.04, p-value = 0.05, respectively). Conclusion: A calendar year difference between patients undergoing IVF treatment at 34 or 35 years of age does not appear to exert any influence regarding outcome. When treatment involves patients above the age of 35, then a single calendar year may exert considerable impact on IVF outcome. This observation indicates that age 35 may serve as a valid cut-off point regarding IVF outcome.

Clinical outcomes of fresh versus frozen embryo transfers and its influence on mid-trimester miscarriage and fetal birth weight: A retrospective study

Aim: The aim of the study was to compare the clinical outcomes of fresh and frozen embryo transfer (FET) in women undergoing assisted reproductive technology and its influence on mid-trimester miscarriage and fetal birth weight.Materials and Methods: The study was conducted between June 2016 and June 2019. The study group comprised 778 cycles, of women, who were undertaken in this retrospective analysis of in vitro fertilization cycles who underwent fresh and FET. These women were randomly divided into two groups, fresh embryo transfers (n = 410) and FETs (n = 368). Both groups were compared with their respective outcome measures such as the clinical pregnancy rates (CPRs), miscarriage rates, multiple pregnancy rates as well as live births and birth weights.Results: The mean age of the participants in fresh and FET groups was 31.13 ± 4.39 and 31.45 ± 4.25, respectively. There were statistically significant differences with respect to clinical pregnancy (P = 0.002) between the groups. Fetal miscarriage rates (30.14% vs. 23.53%) as well as birth weights were not statistically significant (P = 0.164) between fresh versus FET. The results clinically signified that the FET gives a lower miscarriage rate and higher CPRs while not affecting the average fetal birth weight.Conclusion: Adjusting the baseline characteristics and exclusion criteria of participants, women undergoing FET were associated with better clinical outcomes than women undergoing fresh ET cycles Contrary to existing literature, our incidence of neonatal morbidities, or large birth weights were not increased and fetal macrosomia did not occur. Gaining debates on the advantage of frozen over fresh transfers and its effects on obstetric and neonatal outcomes may require a large multicenter pooling of data and analyses.

Influence of Catheter Type and Tenaculum Use on Intrauterine Insemination Outcome.

BackgroundWe investigated the impact of the choice of catheter type and tenaculum use on pregnancy related out- comes in intrauterine insemination (IUI) treatments.Materials and MethodsA total of 338 consecutive IUI cycles were assessed in this retrospective study. Participants were divided according to the insemination technique - soft catheter (group 1; n=175), firm catheter (group 2; n=100), or tenaculum (group 3; n=63). Clinical, laboratory, semen parameters and pregnancy related outcomes were compared.ResultsDemographic characteristics and laboratory parameters were similar between the groups (P>0.05). The clini- cal pregnancy rate (CPR) was significantly higher in the firm catheter (19%, 19/100) and tenaculum (31.7%, 20/63) groups compared to the soft catheter group (5.1%, 9/175, P<0.001). There were no significant differences between the groups in live birth and miscarriage rates per clinical pregnancy (P>0.05).ConclusionOur findings indicate that the use of a firm catheter or tenaculum for IUI might result in a higher CPR, but might not have a considerable effect on the live birth rate (LBR). Further prospective randomized studies are required to determine the long-term effects of the catheter type or tenaculum use on IUI success.

Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome.

Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome.

Randomized, Controlled Pilot Study of Low-Dose Human Chorionic Gonadotropin Administration Beginning From the Early Follicular Phase for Women With Polycystic Ovarian Syndrome Undergoing Ovarian Stimulation Using the Progesterone Protocol.

Purpose: To illustrate whether low-dose human chorionic gonadotropin (hCG) administration during the early follicular phase could reduce the number of large preovulatory follicles in women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation using the progesterone protocol.Methods: We performed a randomized, controlled pilot trial at a university-affiliated tertiary hospital. A total of 40 infertile women undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment with the freeze-all strategy were included. Human menopausal gonadotropin (hMG) and progesterone soft capsule 100 mg/d were added simultaneously beginning from menstrual cycle day 3 for all participants. Low-dose hCG (200 IU) was injected every 3 days in the study group from the first day of ovarian stimulation until trigger. The primary outcome was the number of large preovulatory follicles. Secondary outcomes included the incidence of ovarian hyperstimulation syndrome (OHSS); the number of oocytes retrieved, mature oocytes, and good-quality embryos; and clinical results after frozen-thawed embryo transfer (FET) cycles.Results: The study group had slightly more large preovulatory follicles than the control group (17.75 ± 10 vs. 13.2 ± 5.34; P > 0.05). None of the participants experienced severe OHSS. There were no statistically significant differences in the number of oocytes retrieved (15.9 ± 8.46 vs. 15.75 ± 6.96), mature oocytes (13.55 ± 6.56 vs. 13.4 ± 6.34), and good-quality embryos (5.5 ± 3.41 vs. 4.9 ± 2.99) between the two groups (P > 0.05). Clinical pregnancy rates (65.52 vs. 41.94%; P = 0.067) and live birth rates (48.28 vs. 35.48%; P = 0.315) per transfer following FET of the study group were higher than those of the control group, but without statistical significance.Conclusions: Administration of low-dose hCG from the early follicular phase for PCOS patients undergoing ovarian stimulation with progesterone protocol may lead to slightly more early preovulatory follicles and marginally, but not significantly, higher clinical pregnancy rates. A continuous trial should be performed to explore the effects of supplementation with different doses of hCG from the start of ovarian stimulation in PCOS patients using the progesterone protocol.Clinical Trial Registration: Chictr.org.cn, identifier: ChiCTR-IOR-15007165

The Non-linear Association Between Serum Level of Anti-M�llerian Hormone and in vitro Fertilisation Outcome

Aim of the study was to analyse the relationship between Anti-M�llerian Hormone (AMH) serum level and in vitro fertilisation (IVF) with and without intra-cytoplasmic sperm injection (ICSI) outcome. We performed a retrospective study which included 1073 patients (mean age 34.68�4.28 years, mean body mass index 22.7�15.65 kg/m2) who performed IVF or IVF/ICSI between January 2013 and December 2016.We found that AMH serum level was age-independent positively related with oocytes (beta=0.329, p[0.0001) and zygotes number (beta=0.248, p[0.0001) and negatively correlated with fertilization rate (beta=-0.108, p=0.001). In multivariate regression, after adjustment for confounders, only oocytes number, but not AMH serum level, was associated with zygotes number (beta=0.814, p[0.0001) and fertilisation rate (beta=- 0.133, p=0.001). Patients with AMH in the range 1.1-5 ng/mL had significantly higher biochemical (65.3% versus 56.6%, p=0.009) and clinical pregnancy rates (57.7% versus 49.2%, p=0.014) in comparison with patients with AMH below 1.1 ng/mL and higher clinical pregnancy rates in comparison with patients with AMH above 7 ng/mL (57.7% versus 44%, p=0.011). Logistic regression analysis showed that AMH was positively associated with biochemical (OR 1.19, p=0.003) and clinical pregnancy (OR 1.16, p=0.009) independently of age and number of good embryos transferred in patients with AMH below 5 ng/mL. In turn, when only patients with normal ovarian reserve were analysed (AMH above 1.1 ng/mL), we found an age-independent negative association between AMH and clinical pregnancy (OR 0.93, p=0.014). AMH serum level is associated with both quantitative response (oocytes number) and qualitative parameters (pregnancy rate) during IVF/ICSI. We also found a bimodal relationship between AMH and pregnancy rates, which were positively associated in patients with AMH below 5 ng/mL, although higher AMH values seem to have a negative impact on pregnancy chances.

Factores asociados a embarazo clínico en inseminación intrauterina

Introducción. La inseminación intrauterina es parte de las estrategias del manejo inicial en parejas con infertilidad. Su efectividad en la búsqueda de embarazo ha sido poco investigada y conocida en nuestro país, por lo que es importante definir los grupos de pacientes, indicaciones y condiciones asociadas a una mayor tasa de embarazo clínico. Objetivo. Definir los factores asociados a embarazo clínico en la inseminación intrauterina. Métodos. Estudio retrospectivo de 633 parejas con diagnóstico de infertilidad atendidas en el Centro de Fertilidad y Ginecología del Sur, Cusco, Perú. Se realizaron 1 053 ciclos de inseminación intrauterina, en ciclos espontáneos o asociados a estimulación ovárica, con inseminación doble o simple, inseminación pre o post ovulatoria, con muestra de semen del cónyuge capacitada por swim-up o por gradientes de densidad. Resultados. La tasa de embarazo clínico fue 8,2% por ciclo de inseminación y 13,6% por pareja. Los factores con mayor asociación al embarazo clínico fueron: contar con 2 folículos o más (OR: 2,873), lograr la inseminación sin dificultad (OR: 2,341), tener 3 años o menos de infertilidad (OR: 2,240), el factor cervical como indicación (OR: 2,194), uso de gonadotropinas (OR: 1,846) y edad de la mujer menor a 38 años (OR: 1,819). Conclusiones. La inseminación intrauterina logró una tasa de embarazo clínico aceptable en nuestro estudio, requiriendo ser acompañada de una adecuada selección y preparación de las parejas.

Development of assisted reproductive technology services in Thailand between 2008 and 2014 before the new law: Results generated from the National ART Registry, Royal Thai College of Obstetricians and Gynecologists

Abstract Background While the assisted reproductive technology (ART) relieves the burden of infertility in many couples, it presents significant public health challenges due to the substantial risk for multiple birth delivery and preterm birth, which are associated with poor maternal and fetal health outcomes. For this reason, it is important to monitor the development and effectiveness of ART services in Thailand. Objective To analyze the trends of ART services in Thailand between 2008 and 2014. Methods ART clinics in Thailand are required to submit data to the Royal Thai College of Obstetricians and Gynecologists via the National Reporting System. The data from 2008 to 2014 were collected and analyzed. Results The number of ART centers was increased from 35 to 47. The total fresh ART cycles were also increased from 3,723 to 6,516. The percentage values of intracytoplasmic sperm injection (ICSI), in vitro fertilization, gamete intrafallopian transfer, and zygote intrafallopian transfer cycles were changed from 77.87 to 95.59, 21.43 to 4.31, 0.21 to 0.09, and 0.45 to 0.05, respectively. The clinical pregnancy rates were 28.79–33.19, 22.84–51.34, 14.29–42.86, and 0.00–26.67, respectively. The clinical pregnancy rates in fresh vs. frozen-thawed cycles were 31.01–36.33 vs. 31.54–37.34 (P &lt; 0.05). The clinical pregnancy rates in female age &lt;35 vs. 35–39 vs. ≥40 years were 36.97–40.70 vs. 32.74–33.42 vs. 21.08–31.34, respectively (P &lt; 0.001), and the percentage values of multifetal pregnancy rate were 18.75 vs. 13.30 and 13.69, respectively (P &lt; 0.001). There were increasing preimplantation genetic screening (PGS) cycles, with the percentage of the clinical pregnancy rate (25.90–42.63, P &lt; 0.05). The clinical pregnancy rates in medium-sized ART centers (100–300 cycles per year) vs. in small and large centers were 30.79–41.14 vs. 28.01–34.04 and 8.70–40.35, respectively (P &lt; 0.001). Trends of increasing percentage of ART birth rate to total birth rate ratio were 0.24–0.34 (P &lt; 0.05). Conclusions There were higher clinical pregnancy rates in frozen-thawed cycles. Higher multifetal pregnancy rate and clinical pregnancy rate were also found in younger females. There were increasing uses of ICSI and PGS. A trend toward increasing ART birth to total birth ratio was observed.

NGS euploid embryos have higher delivery rates than those diagnosed as euploid by aCGH/SNP

To review outcomes of all STEET procedures based on PGT-A platform used to determine Ploidy status. Retrospective review of all STEET procedures over an 8 year period at a single center. More than 3200 STEET procedures performed over an 8 year period (2011 to 2018) at a single center were reviewed based on the PGT-A platform (NGS, aCGH or SNP) utilized. Our main outcome measures were: Implantation Rate (IR), Clinical Preg rate (FH) and Live Birth (LB) rate. Only embryos reported as euploid were included in the analysis- embryos reported as mosaic or those not yielding a result were omitted. Statistical significance was determined using contingency X2 with 1 degree of freedom. TABLE 1. Comparison of STEET outcomes depending on PGT-A PlatformTabled 1NGS1aCGH + SNP2SignificanceAverage age at Freeze36.60±4.3436.54± 4.60NSImplantation rate (sacs/embryo)70.1% (1330/1897)62.4% (858/1375)P < 0.00001Clinical Preg rate (FH/embryo)66.7% (266/1897)55.9%(768/1375)P < 0.00001SAB/ Clin Preg10.3% (87/845)12.6% (97/770)NSLive Births3 (Live born/embryo)61.7% (750/1216)53.2%(657/1235)P = 0.0000221 Only included FETs of embryos with NGS performed in the Fresh IVF cycle.2 SNP cases were included with aCGH due to low number3 Live Birth rate calculated through 2017 only (results for 2018 cycles pending) Open table in a new tab 1 Only included FETs of embryos with NGS performed in the Fresh IVF cycle. 2 SNP cases were included with aCGH due to low number 3 Live Birth rate calculated through 2017 only (results for 2018 cycles pending) STEET following PGT-A via NGS resulted in a significantly higher IR compared to aCGH /SNP combined (70.1% vs 62.4%). Similarly, ongoing Pregnancy rates and LB rates were significantly improved when NGS was utilized vs aCGH or SNP. SAB rates were not significantly different between platforms but all methods reduced SAB rates compared to age matched controls without PGS (18% ) (Ref 1). STEET results in high IR, high clinical pregnancy rates and high LB rates across all age groups. However, with advances in PGT-A platforms we can continue to improve outcomes and increase safety of ART by maximizing the potential of every ET procedure. With continuing development of PGT-A platforms and interpretation methods used to determine ploidy we can further improve outcomes and safety by transferring a single embryo with the highest implantation potential every time.

The effect of repeated controlled ovarian stimulation cycles on the gamete and embryo development.

The aim of this study was to investigate if there is an adverse effect of multiple controlled ovarian stimulation (COS) on the maturity of oocytes (MI and MII), fertilization rate, embryo developmental qualities and clinical pregnancy rates in donation cycles. In total, 65 patients undergoing oocyte donation cycles multiple times were included in this study. Patients were grouped as group A that consisted of donors with ≤2 stimulation cycles while B consisted of donors with ≥3 stimulation cycles; and group C included donors who had ≤15 oocytes, while group D had donors with ≥16 oocytes. Numbers of oocytes obtained, MI and MII oocytes, fertilization, embryo quality and clinical pregnancy outcomes were compared. Significant statistical differences were observed in total number of oocytes obtained, maturity of oocytes (MI and MII), fertilization rate, embryo qualities and clinical pregnancy outcomes of donors in groups A-D. Donors with ≤2 ovarian stimulation cycles had lower numbers of immature oocytes than donors with three or more stimulation cycles. However, donors with ≥3 stimulation cycles had higher numbers of mature oocytes, zygotes, with better day 3 embryo qualities and higher clinical pregnancy rates than donors with ≤2 stimulation cycles. Repeated COS does not seem to have any adverse effect on ovarian response to higher dose of artificial gonadotropin, as quality of oocytes collected and their embryological developmental potential were not affected by the number of successive stimulation cycles. The effect of multiple COS on the health of the oocyte donor needs to be assessed for future purpose.

8. COMPARISON OF NATURAL CYCLES VERSUS HORMONE REPLACEMENT TREATMENT FOR 2398 FROZEN–THAWED EMBRYO TRANSFER CYCLES FOR PREIMPLANTATION GENETIC TESTING PATIENTS

Introduction Multiple studies have been performed to evaluate the efficiencies of various endometrial preparation protocols. However, to date, the most appropriate method of endometrial preparation for frozen-thawed embryo transfer (FET) remains debated. To our knowledge, there are no studies comparing FET cycle endometrial preparation protocol for PGT patients, and this study is the first study to compare FET cycle endometrial preparation protocols for PGT patients. Material & methods This retrospective analysis included 2398 FET cycles for 1497 preimplantation genetic testing (PGT) patients with regular menstrual cycles who underwent frozen-thawed single blastocyst transfer from January 2014 to December 2017. The patients were divided into two groups according to the method of endometrial preparation for FET: 586 cycles were natural cycles(NC), and 1812 cycles were hormone replacement treatment (HRT). Reproduction-related clinical outcomes of the two groups were compared. Results The NC group showed a higher clinical pregnancy rate (54.78% vs 51.66%, P=0.188) and live birth rate (45.22% vs 43.21%, P=0.394) than did the HRT group, but these differences were not statistically significant. Moreover, endometrial thickness was significantly greater in the NC group (9.91±2.05 mm vs 8.95±1.53 mm, P Conclusion Our study shows a trend towards higher pregnancy rate and live birth rate for NC compared to HRT. Large randomized controlled trials are warranted to confirm this trend. Additionally, NC is safer than HRT, avoiding ectopic pregnancy and adverse obstetric outcomes.

Ovulation induction: comparing success rates between anovulatory and ovulatory cycles using different treatment protocols

The management of patients with sub-fertility, particularly unexplained sub-fertility, is a sensitive and complex matter. This was a prospective observational study conducted from October 2016 to March 2017 in Galway, Ireland, the aim of which was to identify the clinical pregnancy rates (CPR) in women undergoing ovulation induction (OI) with timed sexual intercourse (TSI) or intrauterine insemination (IUI) and to compare them across two groups: (1) Anovulatory women and (2) ovulatory women with unexplained subfertility. Patients undergoing OI were recruited consecutively and OI regimens were prescribed as per local clinical protocol. The main observation was a higher CPR in the anovulatory group (18%) compared with the ovulatory group (CPR = 10%) (p < 0.05). No difference was observed in the CPR between the TSI and IUI groups. There are many studies to support the use of OI in the treatment of women with anovulatory subfertility, though the use of OI in ovulatory women is a more controversial issue. The treatment options offered to these patients need to be individualized to each couple and should consider their length of infertility, age, and financial means. Due to the lower cost and the less invasive nature of OI-treatment we conclude that a short treatment course could be offered as an acceptable alternative prior to IVF.

The relationship between chromosomal mosaicism and maternal age in embryos TESTED WITH Next Generation Sequencing (NGS) platform

Introduction Chromosomal mosaicism refers to the presence of two or more cell lines with a differentchromosome content in an individual or tissue sample. Besides aneuploidy, the use of highresolution NGS for Pre-implantation Genetic Diagnosis (PGS) detects the presence of mosaicism introphectoderm biopsies. The transfer of mosaic embryos has been shown to result in lowerimplantation rates and higher miscarriage rates as compared to euploid transfer. This study aims to evaluate whether there is an association between mosaicism and maternal ageand the clinical pregnancy and implantation rate of mosaic embryos transfer. Materials and Method A retrospective observational study of 533 blastocyst-stage embryos analysed by NGS from IVFcycles from Sunfert International Fertility Centre over the course of 2015 to 2016 was performed. Ofthose analysed, 197 blastocysts were transferred. The clinical outcome obtained after the transfer ofwhole chromosomal mosaic embryos was compared with those resulting from a control group 190euploid blastocysts. Blastocyst-stage embryos underwent biopsy and trophectoderm cells were extracted for aneuploidyscreening using IIlumina NGS protocol. Mosaic information for each chromosome was obtained. Forthis study, only whole chromosomal mosaicism was considered; segmental mosaicism wascategorized as euploid embryos. These embryos were further stratified by maternal age group. Result The transfer of mosaic embryos resulted in higher clinical pregnancy rate (60% vs 57.5%) andimplantation rate (57% vs 52.9%) compared to euploid embryos. In our series, no miscarriage wasreported in this group of patients. Conclusion In concordance with most published studies, we found that mosaicism is not associated withadvanced maternal age. Unlike aneuploidy which arises from meiotic error, mosaicism on the otherhand is caused by impaired mitotic chromosome segregation which does not appear to increase withadvancing maternal age. Therefore, while there is a direct relationship between advanced maternalage and aneuploidy, age is not a contributor to mosaicism. Contrary to the experience of other groups, we have observed similar rate of implantation in mosaicembryo transfers as compared to euploid embryo transfers. This may be the consequence of thesmall sample size of mosaic embryos transfer (<10% of total blastocysts transferred) in our series. Similarly, no miscarriage was reported. PGS in its current form does have limitations. Implantation rates can potentially be further improvedby developing a clearer understanding of the impact of mosaic embryos. Chromosomal mosaicism refers to the presence of two or more cell lines with a differentchromosome content in an individual or tissue sample. Besides aneuploidy, the use of highresolution NGS for Pre-implantation Genetic Diagnosis (PGS) detects the presence of mosaicism introphectoderm biopsies. The transfer of mosaic embryos has been shown to result in lowerimplantation rates and higher miscarriage rates as compared to euploid transfer. This study aims to evaluate whether there is an association between mosaicism and maternal ageand the clinical pregnancy and implantation rate of mosaic embryos transfer. A retrospective observational study of 533 blastocyst-stage embryos analysed by NGS from IVFcycles from Sunfert International Fertility Centre over the course of 2015 to 2016 was performed. Ofthose analysed, 197 blastocysts were transferred. The clinical outcome obtained after the transfer ofwhole chromosomal mosaic embryos was compared with those resulting from a control group 190euploid blastocysts. Blastocyst-stage embryos underwent biopsy and trophectoderm cells were extracted for aneuploidyscreening using IIlumina NGS protocol. Mosaic information for each chromosome was obtained. Forthis study, only whole chromosomal mosaicism was considered; segmental mosaicism wascategorized as euploid embryos. These embryos were further stratified by maternal age group. The transfer of mosaic embryos resulted in higher clinical pregnancy rate (60% vs 57.5%) andimplantation rate (57% vs 52.9%) compared to euploid embryos. In our series, no miscarriage wasreported in this group of patients. In concordance with most published studies, we found that mosaicism is not associated withadvanced maternal age. Unlike aneuploidy which arises from meiotic error, mosaicism on the otherhand is caused by impaired mitotic chromosome segregation which does not appear to increase withadvancing maternal age. Therefore, while there is a direct relationship between advanced maternalage and aneuploidy, age is not a contributor to mosaicism.

Clinical outcome: the relationship between mosaicism and advanced maternal age with the use of Next Generation Sequencing (NGS)

Introduction Chromosomal mosaicism refers to the presence of two or more cell lines with a different chromosome content in an individual or tissue sample. The implementation of high resolution NGS for PGS has provided more information that it is not only used for embryonic aneuploidy screening, butdetects the presence of mosaicism in trophectoderm biopsies. Recent studies have shown that transfer of mosaic embryos resulted in lower implantation rates and higher miscarriage rates as compared to euploid transfer. This study aims to evaluate whether there is an association between chromosomal mosaicism and advanced maternal age. It also aims to compare the clinical pregnancy and implantation rate between euploid and whole chromosomal mosaic embryos transfer. Materials and Method Retrospective observational study of 533 blastocyst-stage embryos analysed by NGS from IVF cycles from Sunfert International Fertility Centre over the course of 2015 to 2016. Of those analysed, 197 blastocysts were transferred. The clinical outcome obtained after transfer of whole chromosomal mosaic embryos was compared with those resulting from a control group of 190 euploid blastocysts. Blastocyst-stage embryos underwent biopsy and trophectoderm cells are extracted for aneuploidy screening using IIlumina NGS protocol. Mosaic information for each chromosome was obtained. For this study, only whole chromosomal mosaicism is considered; segmental mosaicism were categorized under euploid embryos. These embryos were further stratified by maternal age group: 40 yo. Result Results are summarized in Figure 1. The result showed that mosaicism rates did not vary with advancing maternal age, staying at an average of 10.14%. Euploid and aneuploidy embryos, however, did show changes in regards to age factor as the former displayed a descending trend whereas the latter displayed an increasing trend. Download : Download high-res image (189KB) Download : Download full-size image Figure 1. Percentages of euploid, aneuploid and whole chromosomal mosaic embryos by age groups. Transfer of mosaic embryos resulted in higher clinical pregnancy rate (60% vs 57.5%) and implantation rate (57% vs 52.9%) than euploid embryos. No incidence of miscarriage was reported. Conclusion In accordance to most of the studies published, our findings showed that mosaicism is not associated with advanced maternal age. Unlike aneuploidy which arises from meiotic error, mosaicism, on the other hand is caused by impaired mitotic chromosome segregation which does not appear to increase with advancing maternal age. Therefore, while there is a direct relationship between advanced maternal age and aneuploidy, age is not a contributor to mosaicism. On the contrary, our findings showed conflicting result in the implantation rate of mosaic embryos. Similar rate of implantation as compared to euploid transfer embryos was found in our clinical study whereas in general, transfer of mosaic embryos have lower implantation rate. This might be the consequence of small sample size of mosaic embryos transfer (

Selecting single euploid blastocysts for transfer with NGS significantly improves IVF treatment outcomes: a randomized study

Introduction Recent advancements in whole genomic amplification (WGA) and next-generation sequencing (NGS) have provided new methods for preimplantation genetic testing for aneuploidy (PGT-A) of human embryos derived from in vitro fertilization (IVF) cycles. The present study aimed to investigate the effects of NGS on clinical and ongoing pregnancy outcomes of single embryo transfer (SET) for IVF patients with a good prognosis. Material and Methods A total of 247 IVF patients at mean age 31.4 ± 3.2 years who met the inclusion criteria (under 35 years old with normal uterine lining and normal karyotype) were randomized into two groups: 1) Group A (MA+NGS): patients (n=124) had blastocysts evaluated with morphological assessment (MA) and analyzed with NGS (Yikon Genomics, China; Illumina, USA) and 2) Group B (MA): patients (n=123) had blastocysts evaluated with morphological assessment (MA) only. One blastocyst was selected and transferred to individual patients based on NGS and morphological assessment (Group A) or morphological assessment alone (Group B). Clinical and ongoing pregnancy (≥20 weeks of gestation) rates were compared between the two groups. Results There were no significant differences in female patient's mean age, Day 3 FSH, AMH, E2, antral follicle number between the two groups (p>0.05). NGS identified single euploid blastocysts for transfer and resulted in significantly higher clinical pregnancy rates per transfer in Group A compared to morphological assessment alone in Group B (71.7% vs. 52.1%, respectively, p =0.001). The ongoing pregnancy rates per transfer also significantly increased in Group A compared to Group B (69.2% vs. 46.3%, respectively, p =0.002). There were no twin or multiple pregnancies in both groups. Conclusions While NGS has been recently introduced to IVF treatment, this is the first randomized clinical study showing that there is clinical benefit of NGS for selecting single blastocysts for transfer for good prognosis patients in comparison to morphology assessment alone. With the observed high accuracy of 24-chromosome testing and the improved clinical and ongoing pregnancy outcomes, NGS has demonstrated an efficient, robust high-throughput technology for selecting single blastocysts for transfer for IVF patients with a good prognosis to reduce multiple pregnancies.