In Vitro Fertilization Outcomes Research Articles

Serum Progesterone Levels on the Day of Human Chorionic Gonadotrophin Trigger, and its effects on the Outcome of In Vitro Fertilization, and Embryo Transfer: A Two-Center Study

Abstract Introduction: Gonadotrophin-releasing hormone analogs were expected to make preovulatory progesterone (P4) elevation rare during in vitro fertilization (IVF) cycles, but despite its widespread use, subtle rise in P4 levels on the day of ovulation trigger has a documented prevalence of 5%–38%. The effect of preovulatory progesterone levels on IVF outcomes is still controversial and published data from West Africa is sparse. Materials and Methods: This was a prospective observational study of 107 women who underwent IVF in both Garki and Nisa hospitals in Abuja, Nigeria. A serum sample was obtained from participants on the day of human chorionic gonadotrophin administration for a single determination of progesterone level. Oocytes retrieved, biochemical pregnancy, and clinical pregnancy were the primary outcomes. Results: The mean P4 on human chorionic gonadotrophin (hCG) trigger day was 2.07 ± 0.24 ng/mL and 48 (44.9%) had P4 > 1.5 ng/mL. There was no relationship between P4, and the number of oocytes retrieved but implantation, biochemical pregnancy, and clinical pregnancy were significantly diminished when P4 >1.5 and <1 ng/mL: biochemical pregnancy (27.3% vs. 61.5% vs. 14.6%, χ2 = 17.896; P < 0.0001), clinical pregnancy (24.2% vs. 50.0% vs. 14.6%, χ2 = 11.041; P = 0.004). Conclusion: Pregnancy rates are diminished when P4 on hCG trigger day is elevated.

Correlation of IVF outcomes and number of oocytes retrieved: a UK retrospective longitudinal observational study of 172 341 non-donor cycles

ObjectiveHow do numbers of oocytes retrieved per In vitro fertilisation (IVF) cycle impact on the live birth rate (LBR) and multiple gestation pregnancy (MGP) rates?DesignRetrospective observational longitudinal study.SettingUK IVF clinics.PopulationNon-donor...

Transfer of the fittest: using preimplantation genetic testing for aneuploidy to select embryo(s) most likely to lead to live birth

Preimplantation genetic testing for aneuploidy (PGT-A) was developed to identify euploid embryos from a cohort of embryos with unknown ploidy produced during an invitro fertilization (IVF) cycle. In recent years, the ability of PGT-A to improve IVF outcomes has come into question. The goal of this review was to summarize the major randomized controlled trials (RCTs) and nonselection studies evaluating the benefit of PGT-A to improve the live birth rates (LBRs). We argue that the LBR per transfer is more relevant to the individual patient than the cumulative LBR as a means to minimize the burden of IVF by reducing futile transfers, pregnancy losses, and ongoing aneuploidy. The early RCTs demonstrate improved implantation rates and LBRs with PGT-A for embryo selection vs. traditional morphology. However, these studies are limited by the small sample size and a bias toward good-prognosis patients. Further studies using next-generation sequencing found more variable results but did confirm an improvement in the LBRs per transfer in an older population with a higher baseline risk of aneuploidy. The largest RCT to date showed similar cumulative LBRs in the PGT-A and control groups after biopsy and sequential transfer of up to 3 blastocysts with a significant reduction in the cumulative clinical pregnancy loss rate in the PGT-A group. Nonselection studies evaluating pregnancy outcomes after transfer of euploid vs. aneuploid embryos demonstrate near-perfect negative predictive value for an aneuploid result to predict live birth. Putative mosaic embryos had similar LBRs compared with euploid embryos. The available RCTs and nonselection studies support the practice of using PGT-A to identify euploid embryos for transfer, especially in an older population, while simultaneously selecting against aneuploid embryos, without negative impact on the total reproductive potential of the cycle.

Past COVID-19: The Impact on IVF Outcomes Based on Follicular Fluid Lipid Profile

Follicular fluid is an important component of follicle growth and development. Negative effects of COVID-19 on follicular function are still open. The aim of this work was to study the features of the lipid profile of follicular fluid and evaluate the results of the in vitro fertilization (IVF) program in women after COVID-19 to identify biomarkers with prognostic potential. The study involved samples of follicular fluid collected from 237 women. Changes in the lipid composition of the follicular fluid of patients who underwent COVID-19 in mild and severe forms before entering the IVF program and women who did not have COVID-19 were studied by mass spectrometry. Several lipids were identified that significantly changed their level. On the basis of these findings, models were developed for predicting the threat of miscarriage in patients who had a severe course of COVID-19 and models for predicting the success of the IVF procedure, depending on the severity of COVID-19. Of practical interest is the possibility of using the developed predictive models in working with patients who have undergone COVID-19 before entering the IVF program. The results of the study suggest that the onset of pregnancy and its outcome after severe COVID-19 may be associated with changes in lipid metabolism in the follicular fluid.

Impact of the number of retrieved oocytes on IVF outcomes: oocyte maturation, fertilization, embryo quality and implantation rate

The process of oocyte retrieval represents a key phase during the cycles of in vitro fertilization (IVF). It involves controlled ovarian stimulation to retrieve the highest number of oocytes possible. According to many previous studies, the higher the number of oocytes the higher the chances of obtaining embryos for multiple transfers. In this study, in total, 1987 patients were retrospectively reviewed to investigate the correlations between the number of retrieved oocytes and the subsequent IVF outcomes. Patients were divided into three groups according to the number of retrieved oocytes (Group 1: ≤5 oocytes; Group 2: 6-15 oocytes; Group 3: ≥15 oocytes). The results showed a significant negative correlation between oocyte number and maturation rate as well as fertilization rate. However, a significant positive correlation was found between oocyte number and the blastulation rate. The implantation rate after fresh embryo transfers was higher in group 2 (6-15 oocytes) compared with group 1 (≤5 oocytes). According to our findings, we conclude that oocyte numbers between 6 and 15 oocytes can result in the highest chances of positive IVF outcomes in terms of embryo quality and fresh embryo transfers with lower risks of ovarian hyperstimulation.

Effects of follicular output rate on cumulative clinical pregnancy rate and cumulative live birth rate in PCOS patients with different characteristics.

We aim to explore the effects of follicular output rate (FORT) on cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR) in polycystic ovary syndrome (PCOS) patients with different characteristics undergoing in vitro fertilization (IVF) treatment. This retrospective study analyzed 454 patients with PCOS undergoing their first IVF cycle at our center from January 2016 to December 2020. FORT was calculated as pre-ovulatory follicle count (PFC) × 100/antral follicle count (AFC). Multivariate regression analyses were conducted to explore the relationships between FORT and CCPR and CLBR. Curve fitting and threshold effect analyses were established to find nonlinear relationships. Effect modification in different subgroups were examined by stratification analyses. Based on the FORT values, individuals were classified into the following three groups: low-FORT group, middle-FORT group and high-FORT group. Multivariate regression analyses revealed that FORT was an independent factor affecting the CCPR and CLBR significantly (OR = 1.015, 95% CI: 1.001, 1.030 and OR = 1.010, 95% CI:1.001, 1.020). Curve fitting and threshold effect analyses showed that the CCPR and CLBR had a positive correlation with FORT when the FORT was less than 70% (OR = 1.039, 95% CI: 1.013, 1.065 and OR = 1.024, 95% CI: 1.004, 1.044). Stratification analyses showed that the CLBR increased by 1.3% with each additional unit of FORT for patients with hyperandrogenic manifestations (OR = 1.013, 95% CI: 1.001, 1.025). Compared with the low-FORT group, in the high-FORT group, CCPR increased 1.251 times for patients with polycystic ovarian morphology, while CCPR and CLBR increased 1.891 times and 0.99 times for those with ovulation disorder, respectively (OR = 2.251, 95% CI: 1.008, 5.028 and OR = 2.891, 95% CI: 1.332, 6.323 and OR = 1.990, 95% CI: 1.133, 3.494). In patients with PCOS, cumulative IVF outcomes have a positive correlation with FORT when the FORT is less than 70%. For PCOS patients with polycystic ovarian morphology, ovulation disorder or hyperandrogenic manifestations, a high FORT could be conductive to achieving better pregnancy outcomes.

COVID-19 infection and vaccine have no impact on in-vitro fertilization (IVF) outcome

To investigate the effect of COVID-19 infection or vaccine on IVF outcome. This is a multicenter retrospective study. Data were collected from all patients treated in the ART units between September and November 2021 after the vaccination of the general population began. Medical records of all patients who had IVF/intracytoplasmic sperm injection (ICSI) were retrospectively reviewed. Patients were categorized into four groups: previously infected by COVID-19, vaccinated by COVID vaccine, previously infected and vaccinated, or neither infected nor vaccinated. Total number of participants 151 (vaccinated only 66, infected only 18, vaccinated and previously infected 34, and control 33. Outcomes (ET on day of trigger, number of oocytes retrieved, quality of oocytes, number of fertilized oocytes, number and quality of embryos, number of embryos transferred, number of embryos frozen, implantation rate and clinical pregnancy rate) were compared between these four groups. Moreover, we compared the outcome before and post infection, as well as before and post vaccine in a group of patients. No evidence was found to suggest that COVID-19 disease or SARS-CoV-2 Vaccine adversely affects Clinical pregnancy rates (positive fetal heartbeat) (OR 0.9, CI 0.5–1.9, OR 1.8, CI 0.9–3.6, respectively) and the following parameters: fertilization rate, implantation rate, positive bHcg) (OR 0.9, CI 0.5–1.8, OR 1.5, CI 0.7–2.9, respectively). Although a limitation of our study is the small comparison groups, and the wide confidence intervals in the Odds Ratio estimates.

The Role of L-Arginine-NO System in Female Reproduction: A Narrative Review.

Accumulating evidence are available on the involvement of l-arginine-nitric oxide (NO) system in complex biological processes and numerous clinical conditions. Particular attention was made to reveal the association of l-arginine and methylarginines to outcome measures of women undergoing in vitro fertilization (IVF). This review attempts to summarize the expression and function of the essential elements of this system with particular reference to the different stages of female reproduction. A literature search was performed on the PubMed and Google Scholar systems. Publications were selected for evaluation according to the results presented in the Abstract. The regulatory role of NO during the period of folliculogenesis, oocyte maturation, fertilization, embryogenesis, implantation, placentation, pregnancy, and delivery was surveyed. The major aspects of cellular l-arginine uptake via cationic amino acid transporters (CATs), arginine catabolism by nitric oxide synthases (NOSs) to NO and l-citrulline and by arginase to ornithine, and polyamines are presented. The importance of NOS inhibition by methylated arginines and the redox-sensitive elements of the process of NO generation are also shown. The l-arginine-NO system plays a crucial role in all stages of female reproduction. Insufficiently low or excessively high rates of NO generation may have adverse influences on IVF outcome.

The Quality and Fertilizing Potential of Red Deer (Cervus elaphus L.) Epididymal Spermatozoa Stored in a Liquid State.

The aim of this study was to assess the quality and fertilizing potential of red deer epididymal spermatozoa stored in a liquid state for up to 11 days (D11). In Experiment 1, sperm quality was determined. In Experiment 2, the efficiency of in vitro fertilization (IVF) and artificial insemination (AI) of stored sperm were evaluated. An analysis of sperm quality on D5 of storage revealed a decrease (p < 0.05) in motility and morphology, and a higher proportion of apoptotic spermatozoa. On D1, D7 and D10, the total motility of sperm for IVF and AI was determined to be 82.6%, 71.0% and 64.8%, respectively. The results of IVF and AI demonstrated that the fertilizing potential of spermatozoa differs between days of storage. The percentage of blastocysts was higher when oocytes were fertilized on D1 (17.4 %) compared to D7 (8.5%) and D10 sperm (10.5%). Differences were noted in the pregnancy rates of inseminated hinds. The insemination with D1, D7 and D10 sperm led to live births (33% from D7 and D10). The results indicate that the quality of red deer epididymal spermatozoa remains satisfactory during ten days of storage in a liquid state, and that these spermatozoa maintain their fertility potential.

Association between hysteroscopic features of chronic endometritis and pregnancy outcomes of patients after in vitro fertilization: a retrospective cohort study

This retrospective cohort study explored the morphological features of chronic endometritis (CE) and pregnancy outcomes during in vitro fertilization (IVF) in women with CE (429) at Yantai Yuhuangding Hospital between January 2017 and September 2018. The primary outcome was the clinical pregnancy rate (CPR). The women displayed haemorrhagic spots (175), hyperaemia (122), micropolyps (75), hyperaemia combined with micropolyps (49) and others (8). The CPR and live birth rate (LBR) were different among the hysteroscopic features of CE in fresh embryo transfer cycles (p = .002, p = .011). The miscarriage and premature birth rates were not significantly different among groups (p > .05). Hyperaemia (0.47 [95% CI, 0.29; 0.77]), micropolyps (0.40 [95% CI, 0.23; 0.72]), hyperaemia combined with micropolyps (0.35 [95% CI, 0.18; 0.69]) and others (0.36 [95% CI, 0.19; 0.69]) were associated with the CPR. In conclusion, the hysteroscopic features of CE are associated with IVF pregnancy outcomes, and there were differences in pregnancy outcomes with different CE hysteroscopic features. IMPACT STATEMENT What is already known on this subject? Chronic endometritis (CE) is associated with adverse pregnancy outcomes such as infertility, premature delivery and miscarriage. CE can reduce the success rate of pregnancy and even lead to obstetric and neonatal complications, and is an adverse factor for the success of in vitro fertilization (IVF). There are different types of CE, but their impact on IVF outcomes is unknown. What the results of this study add? The CPR and LBR were different among the hysteroscopic features of CE in fresh embryo transfer cycles (p = .002, p = .011). The miscarriage and premature birth rates were not significantly different among groups (p > .05). After adjustment, the multivariable analysis showed that hyperaemia (OR = 0.47, p = .002), micropolyps (OR = 0.40, p = .002), hyperaemia combined with micropolyps (OR = 0.35, p = .002) and others (OR = 0.36, p = .002) were associated with the CPR among patients with CE. What the implications are of these findings for clinical practice and/or further research? The hysteroscopic features of CE are associated with IVF pregnancy outcomes, and there were differences in pregnancy outcomes with different CE hysteroscopic features. Hence, women with repeated IVF failure should undergo hysteroscopy to examine for the presence of CE and its nature.

Elevated serum uric acid level is associated with adverse reproductive outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycles: a retrospective cohort study

Serum uric acid levels are elevated in polycystic ovary syndrome, however, the relationship between serum uric acid level and reproductive outcomes in women with polycystic ovary syndrome remains unclear. This study aimed to investigate the association between serum uric acid level and the reproductive outcomes in women with polycystic ovary syndrome undergoing invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles. This was a retrospective cohort study performed at a university-affiliated reproductive medicine center. A total of 1903 women with polycystic ovary syndrome undergoing their first invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles between January 2010 and January 2021 were initially included. The trends for reproductive outcomes in polycystic ovary syndrome across quartiles of serum uric acid levels were assessed. A logistic regression analysis was performed to obtain the odds ratios for invitro fertilization outcomes based on the quartiles of serum uric acid with or without adjusting for potential confounding variables. Using generalized additive models, serum uric acid was further treated as its original continuous property to visualize its nonlinear relationship with invitro fertilization outcomes. The live birth rate was the main outcome. After exclusions, a total of 883 women with polycystic ovary syndrome with their first fresh-embryo transfer cycles were included. In quartiles of serum uric acid levels, there was a significant decreasing trend in the live birth rate from the lowest quartile (Q1: 61.8%) to the highest (Q4:45.9%) (Ptrend=.002). The percentage of low birthweight increased from Q1 (22.3%) to Q4 (31.7%) (Ptrend=.049). Compared with those in Q1, women in Q4 showed a significant lower probability of live birth and clinical pregnancy and a higher risk for low birthweight (all P<.05). Both the unadjusted and adjusted generalized additive models indicated that as the serum uric acid level increased, the probability of clinical pregnancy and the live birth rate exhibited an overall decreasing profile, and the risk for low birthweight showed an increasing profile. An elevated serum uric acid level is associated with decreased probabilities of live birth and clinical pregnancy and an increased risk for low birthweight in women with polycystic ovary syndrome. However, these associations may be confounded by other factors and more well-designed studies are needed to confirm these findings in the future.

Anticardiolipin and/or anti-β2-glycoprotein-I antibodies are associated with adverse IVF outcomes.

The purpose of the study is to evaluate the effects of anticardiolipin (aCL) and/or anti-β2-glycoprotein-I (aβ2GPI) antibodies, namely antiphospholipid antibodies (aPL), on in vitro fertilization (IVF)outcomes. The study group comprised infertile women with aPL undergoing IVF-ET cycles. Controls were infertile women with tubal etiology without aPL. The impact of aPL on reproductive outcomes, such as oocyte quality, embryo quality, and implantation capacity, was compared between the study group and controls. Additionally, peripheral blood T cell subsets, such as T helper (Th)1, Th2, Th17, and T regulatory (Treg) cells and cytokines, were analyzed by the flow cytometry. Differences between the study group and controls were analyzed. A total of 132 infertile women, including 44 women with aPL, and 88 controls were sequentially recruited for this study. Women with aPL had lower numbers of total and perfect/available embryos and lower rates of MII oocytes, blastocyst formation, perfect and available embryos, implantation, clinical pregnancy, and take-home baby. Additionally, imbalanced Th1/Th2 and Th17/Treg ratios, significantly higher levels of serum IL-2, TNF-α, IFN-γ, and IL-17A, and a significantly lower serum IL-4 were noticed in women with aPL compared to controls. Women with aPL such as aCL and/or aβ2GPI antibodies were associated with adverse IVF outcomes. Early screening for aPL and appropriate consultation for couples undergoing IVF should be considered. In addition, underlying immunopathology and inflammatory immune mechanisms associated with aPL should be further explored.

One Side Ovarian Rejuvenation: A Quasi-Experimental Study of the Effect of the Autologous Platelet Rich Plasma in Poor Ovarian Responders in IVF.

The poor ovarian response is the most important limiting factor in the success of in vitro fertilization (IVF). The aim of this study was to evaluate the outcome of intraovarian injection of autologous platelet-rich plasma (aPRP) on the oocyte number and IVF outcomes in poor ovarian responders (POR). This quasi-experimental study was performed from August 2021 to December 2021, in Vali-e-Asr Infertility Clinic affiliated with Tehran University of Medical Sciences, Tehran, Iran. There were 12 POR patients selected based on the criteria of Bologna group 4 who underwent two IVF cycles with similar antagonist regimens in a 70-day-interval. Immediately after the Oocytes Pick-Up (OPU), there was a 4cc of autologous PRP multifocal intramedullary injection done into their right ovaries in the first IVF cycle (case group). On the other hand, their left ovaries were considered as the control group. The patients underwent the second IVF cycle after 70 days. Those who had undergone aPRP experienced a significant increase of the mean of antral follicular count (AFC) (from 1.91±0.79 to 2.50±0.90, p=0.043). There was a significant increase in the number of embryos from the right ovary (intervention group) compared to the left ovary (control group) after PRP, but there was no significant difference in the number of embryos in the right ovary before and after the intervention (from 0.25 ±0.45 to 1.08±0.79, p=0.705). There was no significant change in the number of oocytes, AMH, and FSH in the case and control groups before and after the intervention (p>0.05). According to the results of this study, it seems that in females with POR, intraovarian aPRP had no effect on the outcomes (embryos number, number of oocytes, FSH and AMH level), except for an increase in AFC.

Association of urinary bisphenol A concentrations with in vitro fertilisation outcomes: a systematic review and meta-analysis protocol

IntroductionBisphenol A (BPA) is a common environmental endocrine disruptor. BPA has been reported to be associated with female infertility, which may not only affect natural pregnancy and natural fertility but...

Effects of air pollution on clinical pregnancy rates after in vitro fertilisation (IVF): a retrospective cohort study

ObjectiveTo evaluate the effect of air pollution, from oocyte retrieval to embryo transfer, on the results of in vitro fertilisation (IVF) in terms of clinical pregnancy rates, at two fertility...

Impact of paternal age on IVF and pregnancy outcomes with only normal sperm parameters

ObjectivePrevious reports on advanced paternal age effects on assisted reproductive technology (ART) vary considerably and those on frozen–thawed embryo transfer (FET) are rare. We investigated whether paternal age affects in vitro fertilisation (IVF) and FET pregnancy outcomes. Materials and methods1657 IVF cycles performed from January 2014 to May 2018 were retrospectively investigated excluding cases of poor semen parameters. Paternal and maternal ages were categorised into groups, namely, <35, 35–39 and ≥ 40 years, to compare normal fertilisation (2 PN (pronuclei)) and high-quality blastocyst rates. Furthermore, 741 FET cycles were investigated and pregnancy, live birth and miscarriage rates were compared. ResultsFor the maternal age group (35–39), the 2 PN rate was significantly higher with paternal age group of <35 than groups of 35–39 and ≥ 40 (median%, <35 vs. 35–39 vs. ≥40 = 100.0 vs. 71.4 vs. 77.7; P = 0.005). The miscarriage rate was significantly higher with paternal age group of ≥40 than that of <35 and 35–39 when maternal age was <35 (median %, <35 vs. 35–39 vs. ≥40 = 13.1 vs. 7.8 vs. 33.3; P = 0.038). ConclusionOur findings show that when maternal age was <35, advanced paternal age reduces the normal fertilisation rate and increases the FET miscarriage rate when maternal age was 35–39.

Patients with Recurrent Pregnancy Loss Have Similar Embryonic Preimplantation Genetic Testing Aneuploidy Rates and In Vitro Fertilization Outcomes to Infertility Patients

To evaluate aneuploidy rates and invitro fertilization (IVF)/pregnancy outcomes for patients undergoing IVF and preimplantation genetic testing for aneuploidy (PGT-A) with a recurrent pregnancy loss (RPL) diagnosis compared to infertility diagnoses without RPL. Retrospective cohort study. Academic fertility center. Of 372 patients undergoing IVF/PGT-A between January 2016-December 2018, 294 patients were included in the analysis: 56 patients with an RPL diagnosis and 238 with infertility diagnoses without RPL. None. The primary outcome measured was the embryonic aneuploidy rate. Secondary outcomes included fertilization and blastulation rates, number of blastocysts biopsied, cycles without euploid blastocysts, and rates of pregnancy losses, clinical pregnancies, and live births after a euploid embryo transfer. The cohort included 56 patients with RPL and 238 patients without RPL, including data from their first IVF cycle within the time period. Aneuploidy rates were similar between the groups, with a mean of 55% (±31%) in RPL and 54% (±34%) in non-RPL cycles. Similar rates persisted after controlling for age, ovarian reserve, and infertility diagnosis. Fertilization and blastulation rates, as well as cumulative clinical pregnancy, pregnancy loss, and live birth rates after the transfer of at least one euploid embryo were also similar between the two groups. These results suggest that IVF/PGT-A cycles from patients with an RPL diagnosis have similar IVF and pregnancy outcomes to those of patients with infertility without RPL. This research can help guide counseling for RPL patients considering IVF with PGT-A.

Women’s quality of sleep and in vitro fertilization success

Women undergoing in vitro fertilization (IVF) are emotionally challenged. Anxiety, depression, and sleep disturbances are common complaints. The impact of these symptoms on IVF outcome is however debated. In this study, we aimed at investigating whether sleep quality and psychological health can affect the chances of success of the procedure. Women undergoing IVF were recruited at the time of oocytes retrieval. Women’s sleep quality and psychological health was assessed using the Pittsburgh Sleep Quality Index (PSQI), the Fertility Problem Inventory (FPI), and the Hospital Anxiety and Depression Scale (HADS). Baseline characteristics and results of the three scales were compared between women who did and did not succeed. Overall, 263 women were included, of whom 81 had a clinical pregnancy (31%). As expected, successful women were younger, and their ovarian reserve was more preserved. FPI and HADS scores did not differ. Conversely, a statistically significant difference emerged for the PSQI score, the median [interquartile range] in pregnant and non-pregnant women being 4 [3–5] and 5 [3–7], respectively (p = 0.004). The crude and adjusted OR of pregnancy in women with a PSQI > 5 (indicating impaired sleep quality) was 0.46 (95% CI 0.25–0.86, p = 0.02) and 0.50 (95% CI: 0.26–0.94, p = 0.03), respectively. In conclusion, low sleep quality is common in women scheduled for IVF and could influence the success of the procedure.

The Effect of Stimulation Protocols (GnRH Agonist vs. Antagonist) on the Activity of mTOR and Hippo Pathways of Ovarian Granulosa Cells and Its Potential Correlation with the Outcomes of In Vitro Fertilization: A Hypothesis.

Controlled ovarian hyperstimulation (COH) is essential for the success of in vitro fertilization (IVF). Evidence showing the comparison of different COH protocols remains predominantly of low certainty and derives from unspecified infertile and highly heterogeneous populations. Thus, personalized approaches to examine the response of patients to the various COH protocols need to be investigated. Data from in vitro and animal studies have identified the mechanistic target of rapamycin (mTOR) and Hippo signaling pathways play a key role in follicular homeostasis and oocyte quality. To be specific, current data indicate the controlled activation of mTOR and the controlled inhibition of the Hippo pathway within the ovarian granulosa cells (GC). Both are reported to lead to a nurturing follicular microenvironment, increase oocyte quality, and potentially improve reproductive outcomes. As intracellular markers, phosphorylated/unphosphorylated levels of the pathways’ main downstream mediators could be included among the candidate “personalized” predictors of patients’ response to COH protocols and final IVF outcomes. Based on these hypotheses, we make a preliminary attempt to investigate their validity: We propose a prospective cohort study to compare the levels of certain phosphorylated/unphosphorylated components of the investigated pathways (mTOR, ribosomal protein S6 kinase beta-1 (p70S6K-1), yes-associated protein-1 (YAP-1), and transcriptional coactivator with PDZ-binding motif (TAZ)) within the follicular fluid-isolated GC between women undergoing gonadotropin-releasing hormone (GnRH) antagonist/“short” protocols and those receiving GnRH agonist/“long 21” protocols. A case-control design comparing these levels between women achieving pregnancy and those who did not is further planned. Additional analyses addressing the population’s expected heterogeneity are planned after the completion of the pilot phase, during which 100 participants undergoing IVF are intended to be recruited. At this stage, these hypotheses are solely based on in vitro/animal data, and thus, similar studies on humans in this respect are necessary for the investigation of their potential validity.

The use of frozen embryos and frozen sperm have complementary IVF outcomes: a retrospective analysis in couples experiencing IVF/Donor and IVF/Husband

BackgroundThe cryopreservation of sperm or embryos has been an important strategy in the treatment of infertility. Recently studies have revealed the outcomes after IVF (in vitro fertilization) treatment for single-factor exposure either to frozen sperm or embryos.MethodsThis retrospective study was to uncover the exposure to both frozen sperm and embryo effects using IVF/H (in vitro fertilization using husbands’ fresh sperm) or IVF/D (in vitro fertilization using donors’ frozen sperm) treatment.ResultsThe results showed the clinical pregnancy rate (CPR), live birth rate (LBR) and low birth weight rate (LBW) increased to 63.2% (or 68.1%), 61.1% (or 66.4%) and 15.8% (or 16.2%) after using frozen embryo transfer within Group IVF/H (or Group IVF/D). After using frozen sperm, the high-quality embryo rate (HER) increased to 52% and baby with birth defect rate (BDR) reduced to 0% in subgroup D/ET comparing to subgroup H/ET. While the fertilization rate (FER), cleavage rate (CLR), HER and multiple pregnancy rate (MUR) reduced to 75%, 71%, 45% and 9.2% in subgroup D/FET comparing to subgroup H/FET. Finally, our study found accumulative frozen gamete effects, including both sperm and embryos, led to the significantly increasing in the HER (p < 0.05), CPR (p < 0.001), LBR (p < 0.001) and LBW (p < 0.05) in subgroup D/FET comparing to subgroup H/ET.ConclusionThe use of frozen embryos and frozen sperm have complementary IVF outcomes. Our findings highlighted the parent’s distinguished frozen effect not only for clinical studies but also for basic research on the mechanism of cellular response adaptations to cryopreservation.