Reducing radicality in fertility-sparing surgery is associated with improved in vitro fertilization outcome in early-stage cervical cancer: A national retrospective study.

OBJECTIVE: Fertility-sparing surgery (FSS) aims to achieve oncological outcomes that are non-inferior to radical treatment while preserving fertility and optimizing reproductive results. This study assesses in vitro fertilization (IVF) outcomes in early-stage cervical cancer survivors following FSS, comparing radical and non-radical approaches. METHODS: This retrospective analysis used data from Hungary's National Health Insurance Fund (2004-2022) on patients who underwent IVF treatment following FSS for early-stage cervical cancer at ten Hungarian fertility clinics. Patients were classified into radical and non-radical surgical groups, with the uterine arteries being spared in the non-radical procedures. RStudio (R software version: 4.2.2) was used for statistical analysis. Student's t-test was used to compare group means, and Fisher's exact test was applied to assess independence and distributions between categorical variables, and to estimate odds. RESULTS: The study analyzed data from 122 IVF treatment cycles involving 36 patients. The non-radical group had a significantly higher live birth rate (83%, 5/6 compared to the radical group (17%, 5/30). Additionally, the non-radical group had a significantly higher implantation rate and cumulative live birth rate per oocyte retrieval (37%, 7/19 and 55%, 6/11 respectively) compared to the radical group (8%, 12/148 and 6%, 5/80 respectively). CONCLUSION: This is the largest study to evaluate IVF outcomes in young cervical cancer survivors who have undergone FSS. The findings suggest that less radical procedures are associated with significantly better IVF outcomes. These results emphasize the importance of considering oncological safety and reproductive outcomes together when choosing FSS for early-stage cervical cancer patients. It also highlights the reproductive benefits of performing less radical surgery.

Impact of body mass index on assisted reproductive technology outcomes in patients with polycystic ovary syndrome: a meta-analysis.

The effect of obesity on pregnancy outcomes of patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technology (ART) remains unclear. As such, a meta-analysis of recent studies was conducted to probe the effect of being overweight or obese on ART pregnancy outcomes in patients with PCOS. PubMed, Embase, MEDLINE, Scopus and Web of Science were searched from inception to 22 July 2023 without language restrictions. The main indicators were: live birth rate, clinical pregnancy rate, spontaneous abortion rate and multiple pregnancy rate. Ten studies were analysed, with a combined sample size of 247,845. Among patients with PCOS undergoing ART who were overweight or obese, the live birth rate, clinical pregnancy rate, implantation rate and number of retrieved oocytes were lower than in normal-weight patients with PCOS, and the spontaneous abortion rate was higher than in normal-weight patients with PCOS. Obese patients with PCOS undergoing ART had a lower multiple pregnancy rate and a lower number of mature oocytes compared with normal-weight patients with PCOS. The data showed that, among patients with PCOS, being overweight or obese has a negative effect on ART pregnancy outcomes. This meta-analysis may inform guidelines for pregnancy with ART, and encourage overweight or obese patients with PCOS to lose weight.

Biomarkers Assessing the Role of Cumulus Cells on IVF Outcomes: A Systematic Review.

PURPOSE: Although significant improvements in assisted reproductive technology (ART) outcomes have been accomplished, a critical question remains: which embryo is most likely to result in a pregnancy? Embryo selection is currently based on morphological and genetic criteria; however, these criteria do not fully predict good-quality embryos and additional objective criteria are needed. The cumulus cells are critical for oocyte and embryo development. This systematic review assessed biomarkers in cumulus-oocyte complexes and their association with successful IVF outcomes. METHODS: A comprehensive search was conducted using PubMed, Embase, Scopus, and Web of Science from inception until November 2022. Only English-language publications were included. Inclusion criteria consisted of papers that evaluated genetic biomarkers associated with the cumulus cells (CCs) in humans and the following three outcomes of interest: oocyte quality, embryo quality, and clinical outcomes, including fertilization, implantation, pregnancy, and live birth rates. RESULTS: The search revealed 446 studies of which 42 met eligibility criteria. Nineteen studies correlated genetic and biochemical biomarkers in CCs with oocyte quality. A positive correlation was reported between oocyte quality and increased mRNA expression in CCs of genes encoding for calcium homeostasis (CAMK1D), glucose metabolism (PFKP), extracellular matrix (HAS2, VCAN), TGF-ß family (GDF9, BMP15), and prostaglandin synthesis (PTGS2). Nineteen studies correlated genetic and biochemical biomarkers in CCs with embryo quality. A positive correlation was reported between embryo quality and increased mRNA expression in CCs of genes encoding for extracellular matrix (HAS2), prostaglandin synthesis (PTGS2), steroidogenesis (GREM1), and decreased expression of gene encoding for hormone receptor (AMHR2). Twenty-two studies assessed genetic and biochemical biomarkers in CCs with clinical outcomes. Increased expression of genes encoding for extracellular matrix (VCAN), and TGF-ß family (GDF9, BMP15) were positively correlated with pregnancy rate. CONCLUSION: Genetic biomarkers from cumulus cells were associated with oocyte quality (CAMK1D, PFKP, HAS2, VCAN, GDF-9, BMP-15, PTGS2), embryo quality (GREM1, PTGS2, HAS2), and pregnancy rate (GDF9, BMP15, VCAN). These results might help guide future studies directed at tests of cumulus cells to devise objective criteria to predict IVF outcomes.

Supplementation with vitamin D improves the embryo quality in in vitro fertilization (IVF) programs, independently of the patients' basal vitamin D status.

PURPOSE: The study aims to demonstrate the effects of Vitamin D (VD) supplementation, prior to oocyte pick-up within IVF protocols, in women with diverse VD status at the enrollment. METHODS: A total of 204 women eligible for intra-cytoplasmatic sperm injection (ICSI) cycles were included in the study and two homogeneous groups were selected from the database. Both group of patients with normal VD baseline level (> 40 ng/ml) and patients with low VD baseline level (< 20 ng/ml) were divided into control group and treatment group. The control group followed the standard procedure. The treatment group was supplemented with vitamin D3 as cholecalciferol in combination with Myo-Inositol, folic acid, and melatonin 3 months before standard procedure, once a day in the evening. RESULTS: VD levels significantly increased in the study group of low baseline VD, both in serum and in the follicular fluid compared to controls. The treatment induced a significant improvement of the embryo quality in both group of patients considered. CONCLUSION: Supplementation of VD in patients undergoing ICSI procedures significantly improved the number of top-quality embryos compared with the control group, either starting from VD normal baseline values or starting from low values. TRIAL REGISTRATION NUMBER: 07/2018.

Machine learning-based clustering to identify the combined effect of the DNA fragmentation index and conventional semen parameters on in vitro fertilization outcomes.

BACKGROUND: Previous studies have demonstrated an association between male sperm quality and assisted reproduction outcomes, focusing on the effects of individual parameters and reaching controversial conclusions. The WHO 6th edition manual highlights a new semen assay, the sperm DNA fragmentation index, for use after routine semen examination. However, the combined effect of the sperm DNA fragmentation index (DFI) and routine semen parameters remains largely unknown. METHODS: We assessed the combined effect of the sperm DFI and conventional semen parameters on single fresh conventional IVF outcomes for infertile couples from January 1, 2017, to December 31, 2020. IVF outcomes were obtained from the cohort database follow-up records of the Clinical Reproductive Medicine Management System of the Third Affiliated Hospital of Guangzhou Medical University. An unsupervised K-means clustering method was applied to classify participants into several coexposure pattern groups. A multivariate logistic regression model was used for statistical analysis. RESULTS: A total of 549 live births among 1258 couples occurred during the follow-up period. A linear exposure-response relationship was observed among the sperm DFI, sperm motility, and IVF outcomes. In multivariable adjustment, increased sperm DFI values and decreased sperm motility and semen concentration levels were associated with reduced odds of favourable IVF outcomes. Four coexposure patterns were generated based on the sperm DFI and the studied semen parameters, as follows: Cluster 1 (low sperm DFI values and high sperm motility and semen concentration levels), Cluster 2 (low sperm DFI values and moderate sperm motility and semen concentration levels), Cluster 3 (low sperm DFI values and low sperm motility and semen concentration levels) and Cluster 4 (high sperm DFI values and low sperm motility and semen concentration levels). Compared with those in Cluster 1, participants in Cluster 3 and Cluster 4 had lower odds of a live birth outcome, with odds ratios (95% confidence intervals [CIs]) of 0.733 (0.537, 0.998) and 0.620 (0.394, 0.967), respectively. CONCLUSIONS: When combined with low sperm DFI values, there was no significant difference between high or moderate sperm concentration and motility levels, and both were associated with favourable IVF outcomes. Low sperm parameter levels, even when DFI values remain low, may still lead to poor IVF outcomes. Participants with high sperm DFI values and low sperm motility and semen concentration levels had the worst outcomes. Our findings offer a novel perspective for exploring the joint effects of sperm DFI and routine semen parameter values.

Pituitary suppression with GnRH agonists before ART may be insufficient to treat women with severe adenomyosis.

RESEARCH QUESTION: Does aromatase inhibitor improve IVF outcomes by reducing local oestrogen production in patients with adenomyosis undergoing long-term gonadotrophin-releasing hormone agonist (GnRHa) treatment? DESIGN: Four patients with severe adenomyosis who failed to improve after long-term treatment (≥3 months) with depot GnRHa received treatment with an aromatase inhibitor for 21 days. Blood oestradiol concentrations were monitored after GnRHa treatment both before and after treatment with an aromatase inhibitor. Women received a transfer of IVF autologous or donor oocytes. Pregnancy and ongoing pregnancy rates were the primary outcomes. Blood oestradiol concentration after treatment with an aromatase inhibitor was a secondary outcome. RESULTS: Patients with severe adenomyosis presented with hyperestrogenism due to local production from the lesions even after long-term treatment with GnRHa. Treatment with an aromatase inhibitor reduced hyperestrogenism and improved clinical outcomes in adenomyosis patients who have experienced previous embryo transfer failures. CONCLUSION: Women with severe adenomyosis would benefit from letrozole or a combination of GnRHa plus letrozole before receipt of treatment with assisted reproductive technology. For women with severe adenomyosis, GnRHa treatment alone may be insufficient to suppress oestrogen production by adenomyotic lesions. Thus, it should be mandatory to test for oestradiol concentrations in patients with severe adenomyosis who have received long-term GnRHa treatment. Also, GnRHa may not always be the sole strategy for medical management of adenomyotic lesions. Letrozole is safe and can improve IVF outcomes for patients with adenomyosis.

Adjustment of progesterone administration after endometrial transcriptomic analysis does not improve reproductive outcomes in women with adenomyosis.

RESEARCH QUESTION: Do patients with adenomyosis present a dysregulated endometrial receptivity that can be reversed with personalized embryo transfer (PET) by transcriptomic-based progesterone adjustment, improving IVF outcomes? DESIGN: A multicentre, retrospective, cohort study that transcriptomically analysed the endometrial receptivity of the endometrium in patients with adenomyosis (n = 81) and healthy women (n = 231). Subsequently, implantation, biochemical and clinical miscarriage, and live birth rates between adenomyosis patients with one previous implantation failure using donor oocytes who received (n = 59) or did not receive (n = 66) PET based on endometrial receptivity, were observed to evaluate if adjusted progesterone improves reproductive outcomes of adenomyosis patients. RESULTS: Patients with adenomyosis significantly presented an altered endometrial receptivity (non-receptive) compared with healthy patients (53.1% versus 37.2%, P = 0.0179), elevating the risk of adenomyosis patients having a non-receptive endometrium 42.59% higher (95% CI 41.50 to 44.45). No significant differences were found in implantation (62.7% versus 78.8%, P = 0.0514), biochemical (13.5% versus 3.9%, P = 0.1223) and clinical (10.8% versus 15.4%, P = 0.7543) miscarriage, or live birth rates (75.7% versus 80.8%, P = 0.6066), in patients with PET compared with those without PET. CONCLUSIONS: Women with adenomyosis presented an altered expression of genes involved in decidualization, and a higher rate of non-receptive endometrial statuses than controls. Although progesterone is indispensable for implantation, adjusting progesterone before PET, using endometrial transcriptomic signatures, does not improve IVF outcomes in patients with adenomyosis. Other molecular mechanisms beyond progesterone regulation may be involved in implantation failure.

Comparisons of different treatment outcomes in IVF/ET patients with hydrosalpinx: a retrospective study.

AIMS: To explore suggestions for clinicians on the most effective treatment for hydrosalpinx undergoing IVF-ET. MATERIALS AND METHODS: We reviewed 936 women with hydrosalpinx and 6715 tubal infertile women without hydrosalpinx who underwent IVF/ICSI between January 2014 and August 2019 in our center. Hydrosalpinx patients received different treatments including laparoscopic surgery (only salpingectomy and proximal tubal occlusion/ligation were included), ultrasonic-guided aspiration and hysteroscopic tubal occlusion. Outcomes were analyzed by One-way ANOVA, Chi-Square test and logistic regression. RESULTS: The live birth rate (LBR) of laparoscopic surgery was significantly higher compared with hydrosalpinx aspiration (48.3% vs 39.6%, p = .024). The cumulative live birth rate (CLBR) of subsequent laparoscopic surgery was significantly higher compared with subsequent hysteroscopic occlusion (65.1% vs 34.1%, p = .001) and no subsequent treatment (65.1% vs 44.9%, p < .005). Subsequent laparoscopic surgery significantly improved the CLBR of hydrosalpinx patients who received ultrasonic-guided aspiration and didn't get clinical pregnancy in fresh cycles (Odds Ratio (OR) =1.875; 95%CI = 1.041-3.378, p = .036). CONCLUSIONS: Laparoscopic surgery leads to significantly higher LBR than ultrasonic-guided aspiration and significantly higher CLBR than hysteroscopic occlusion and no treatment.

Embryo transfers performed during daylight savings time led to reduced live birth rates in older patients.

PURPOSE: To study the impact of undergoing an embryo transfer during the week of daylight savings time transition on live birth rates. METHODS: We performed a retrospective observational cohort study of patients undergoing embryo transfer at an academic infertility practice during the week of spring or fall daylight savings time transition (cases), or the 2 weeks preceding and following the daylight savings transition (controls) between 2015 and 2021. The primary exposure was completion of an embryo transfer during the week of daylight savings time transition. The primary outcome was a comparison of live birth rate per embryo transfer among individuals undergoing an embryo transfer during the week of daylight savings time (DST) transition and those who did not. RESULTS: A total of 309 embryo transfers occurred during the week of daylight savings transition and 1242 embryo transfers occurred in the control group outside of the daylight savings transition week. The live birth rate after embryo transfer during DST transition weeks was 39.2% (121/309) compared to 40.8% (507/1242) (p = 0.59). When restricting the analysis to individuals (age > 37 years), the live birth rate after embryo transfer during DST transition week was 23.5% (24/102) compared to 34.8% (149/429) (p = 0.03). This difference persisted in the mixed-effects regression model demonstrating that after adjusting for relevant covariates, embryo transfer during DST transition weeks resulted in a 45% decrease in the odds of achieving a live birth. CONCLUSION: Daylight savings time transition may be associated with less favorable outcomes after embryo transfer among an older infertile patient population. Future work is needed to prospectively examine the influence of circadian rhythm disruption on reproductive outcomes.

Associations between microbial presence in follicular fluid with IVF outcomes: a systematic review and meta-analysis.

PURPOSE: The aim of the study was to synthesize disparate studies to investigate potential impact of microbial presence in FF of infertile women on IVF outcomes. METHODS: Following preliminary searches to find medical subject heading (MeSH) terms plus free terms, a systematic search was performed in the PubMed, Cochrane Library, Embase, Web of Science, and Clinicaltrials.gov databases from January 10, 2022, to July 5, 2023. Data collected for each study were analyzed using RevMan 5.4 software available on the Cochrane website. RESULTS: After correcting for contamination from the vagina, the FFs of 289 women were detected positively by microbial culture and identification, ELISA, and IPA. The pregnancy rate of the FF-positive group was significantly lower than the FF-negative group (19.7% vs. 32.2%) and (OR: 0.57, 95% CI: 0.28-1.14, P=0.11; I2=56%) while the fertilization rate was almost equal (60.0% vs. 62.0%) and (OR: 1.03, 95% CI: 0.88-1.20, P=0.72; I2=0%). Evidence quality was very low. CONCLUSIONS: The different species of microorganisms in FF of infertile women may have different effects on IVF outcomes. The Lactobacillus spp. may have a positive effect, while other microorganisms may have the opposite effect.

Phytoestrogens Present in Follicular Fluid and Urine Are Positively Associated with IVF Outcomes following Single Euploid Embryo Transfer.

The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC-MSMS, both collected on vaginal oocyte retrieval day. These measurements correlated with IVF clinical outcomes. In models adjusted for age, BMI, race/ethnicity, and smoking status, higher FF phytoestrogen concentrations were significantly associated with higher serum estradiol, enhanced probability of implantation, clinical pregnancy, and live birth. Moreover, higher urine phytoestrogen concentrations were significantly associated with improved oocyte maturation and fertilization potential and increased probability of clinical pregnancy and live birth. Finally, higher FF and urine phytoestrogen concentrations were associated with a higher probability of live birth from a given IVF cycle. Our results suggest that dietary phytoestrogens improved reproductive outcomes of women undergoing IVF treatment. However, additional prospective studies are needed to optimize the use of phytoestrogens to further enhance reproductive outcomes and/or protect against reproductive insults.

The Impact of Essential Trace Elements on Ovarian Response and Reproductive Outcomes following Single Euploid Embryo Transfer.

Essential trace elements are required in extremely small amounts and obtained through diet. This research focuses on detecting major trace elements in different biofluids of sixty women undergoing ICSI with PGT-A and SET/FET at IVI-RMA, New Jersey, and assessing their impact on their IVF outcomes. Urine, plasma, and follicular fluid samples were collected on the vaginal oocyte retrieval day to measure the concentrations of eight essential trace elements (copper, zinc, molybdenum, lithium, selenium, manganese, chromium, and iron) using ICP-MS. After analysis, ovarian response and preimplantation outcomes had significant positive associations with both copper alone and the copper/zinc ratio in the follicular fluid and plasma, in addition to plasma manganese. Alternatively, elevated follicular fluid lithium concentrations were significantly associated with poor preimplantation outcomes while the urinary molybdenum concentration was significantly associated with a lower probability of implantation, clinical pregnancy, and live birth. Urinary lithium and chromium concentrations were significantly associated with a lower probability of achieving a live birth. Our results suggest that the essential trace elements present in follicular fluid, plasma, and urine of women are directly associated with their reproductive outcomes, with copper and manganese exerting positive effects and lithium and molybdenum exerting negative effects.

Bioaccumulation of Non-Essential Trace Elements Detected in Women's Follicular Fluid, Urine, and Plasma Is Associated with Poor Reproductive Outcomes following Single Euploid Embryo Transfer: A Pilot Study.

This study aims to determine the association of non-essential trace elements present in follicular fluid, plasma, and urine with reproductive outcomes of women undergoing intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidies (PGT-A) and single frozen euploid embryo transfer (SET/FET). This single-center, prospective cohort study included sixty women undergoing ICSI with PGT-A and SET/FET between 2018 and 2019. Urine, plasma and follicular fluid samples were collected on the vaginal oocyte retrieval day to simultaneously quantify ten non-essential trace elements (i.e., Ba, Sr, Rb, Sn, Ti, Pb, Cd, Hg, Sb, and As). We found several associations between the levels of these non-essential trace elements and clinical IVF parameters. Specifically, the increased levels of barium in follicular fluid were negatively associated with ovarian function, pre-implantation development and embryo euploidy, while elevated strontium concentrations in this biofluid were negatively associated with impaired blastulation and embryo euploidy. Elevated plasma strontium levels were negatively associated with ovarian function, fertilization and blastulation. Enhanced presence of other trace elements in plasma (i.e., rubidium and arsenic) were associated with a diminished ovarian function and limited the number of recovered oocytes, mature oocytes and zygotes, respectively. Fully adjusted models suggested significantly lower odds of achieving a live birth when increased concentrations of barium and tin were found in urine.

Clinical, obstetric and perinatal outcomes after vitrified-warmed euploid blastocyst transfer are independent of cryo-storage duration.

RESEARCH QUESTION: The study aimed to retrospectively evaluate the impact of cryo-storage duration on clinical, obstetric and perinatal outcomes after vitrified-warmed euploid blastocyst transfer. DESIGN: This was an observational study including 2688 vitrified-warmed euploid single blastocyst transfers that was conducted at a private IVF centre between May 2013 and March 2020. It included a total of 1884 women (age 38 ± 3 years) undergoing at least one transfer after preimplantation genetic testing for aneuploidies. The euploid blastocysts transferred were clustered into seven groups according to the cryo-storage duration between vitrification and warming: ≤60 days (n = 646; control group), 61-90 days (n = 599), 91-180 days (n = 679), 181-360 days (n = 405), 361-720 days (n = 144), 721-1080 days (n = 118) and >1080 days (n = 97). The primary outcome was the live birth rate (LBR) per transfer. The secondary outcomes were miscarriage rate, obstetric and perinatal issues. The data were adjusted for confounders through logistic or linear regressions. RESULTS: A significantly lower LBR was reported for transfers performed within 91-180 days (n = 291/679, 42.9%; P = 0.017), 181-360 days (n = 169/405, 41.7%; P = 0.016) and 361-720 days (n = 57/144, 39.6%; P = 0.034) versus ≤60 days (n = 319/646, 49.4%). However, this was mainly due to top-quality embryos being transferred first when more euploid blastocysts were available, thereby leaving lower quality ones for subsequent procedures. Indeed, the multivariate odds ratios adjusted for confounders showed similar results across all cryo-storage duration clusters. No difference was reported also for all secondary outcomes. CONCLUSIONS: Cryo-storage duration even beyond 3 years from blastocyst vitrification does not affect clinical, obstetric and perinatal outcomes.

Interplay of Oxidants and Antioxidants in Mammalian Embryo Culture System.

One principal purpose of assisted reproductive technology (ART) is to produce viable and good quality embryos. However, a variety of environmental factors may induce epigenetic changes in the embryo. Moreover, laboratory conditions including the culture media may also affect embryo development. Therefore, media change is an important factor in maintaining proper oxidant/antioxidant balance during embryo culture. Alterations in the oxidant/antioxidant balance are related to various cellular responses such as an increase in the level of reactive oxygen species (ROS) and consequent lipid peroxidation (LPO), DNA damage, and apoptosis. The current study focuses on the role of external factors on embryo culture and the ability of antioxidants to enhance in vitro fertilization (IVF) outcomes. Indeed, an optimization of media culture by the addition of enzymatic and nonenzymatic antioxidants in animal models and human embryos in ART has been updated in this study, with an emphasis on comparing the available results and their possible reasons.

Effects of oral contraceptive pretreatment on IVF outcomes in women following a GnRH agonist protocol.

RESEARCH QUESTION: Does oral contraceptive pretreatment impact IVF-embryo transfer cycle outcomes in women following the gonadotrophin-releasing hormone agonist (GnRHa) protocol? DESIGN: This retrospective study was designed to compare cycle outcomes after oral contraceptive pretreatment versus the standard protocol in women within the GnRHa long protocol or the GnRHa short protocol. A total of 2052 women undergoing their first IVF treatment with the GnRHa long protocol and 3557 women with the GnRHa short protocol between 2012 and 2017 were enrolled. RESULTS: No significant differences in the rates of clinical pregnancy (long protocol: 49.2% versus 46.7%; short protocol: 39.4% versus 38.0%) or live birth (long protocol: 44.3% versus 41.3%; short protocol: 32.8% versus 31.4%) after fresh embryo transfer were observed between the oral contraceptive group and the control group in either the long protocol or the short protocol. CONCLUSIONS: Oral contraceptive pretreatment has no effect on IVF outcomes in either the GnRHa long protocol or short protocol.

Effect of endometrial injury on in vitro fertilization pregnancy rates: a randomized, multicentre study.

PURPOSE: To determine if endometrial injury prior to the first or second in vitro fertilization (IVF) cycle affects clinical pregnancy rates. METHODS: This study was a randomized, multicentre, controlled study performed at three Canadian outpatient fertility clinics. Patients undergoing their first or second IVF cycle were randomized to a single endometrial injury 5-10 days prior to the start of gonadotropins in an IVF cycle compared to no injury. The primary outcome was clinical pregnancy rate. Secondary outcomes were live birth rates, implantation rate, endometrial thickness, number of oocytes retrieved and the rate of embryo cryopreservation. RESULTS: Fifty-one women were randomized (25 in the en dometrial injury group and 26 in the control group); however, the study was terminated prematurely due to slow recruitment (target 332 patients). Groups were similar at baseline for: age, duration of infertility, BMI, day 3 FSH, and the number having first IVF cycle. The groups were similar for gonadotropin dose, endometrial thickness, number of oocytes retrieved, and embryo cryopreservation rate. The clinical pregnancy rate in the endometrial injury group was 52% (13/25) and 46% (12/26) in the control group (p = 0.45). Live birth rate in the endometrial injury group was 52% (13/25) and 35% (9/26) in the control group (p = 0.17). The implantation rate was also similar (58% vs. 45%, p = 0.17). CONCLUSIONS: This study did not detect a difference in implantation, clinical pregnancy or live birth rates; however, the lack of difference in this study may be because it was underpowered. CLINICAL TRIALS REGISTRATIONS: gov: NCT01983423.

Volatile organic compounds and good laboratory practices in the in vitro fertilization laboratory: the important parameters for successful outcome in extended culture.

PURPOSE: This study aims to describe the role of implementing good laboratory practices to improve in vitro fertilization (IVF) outcomes which are of great interest for practitioners dealing with infertility. METHODS: Certain modifications were introduced in May 2015 in our IVF laboratory like high-efficiency particulate air CODA system, steel furniture instead of wooden, use of new disinfectants like oosafe, and restriction of personnel entry along with avoidance of cosmetics like perfume to improve pregnancy rates. Volatile organic compound (VOC) meter reading was monitored at two time points and five different places in the laboratory to compare the embryonic development parameters before (group A: July 2014-April 2015) and after (group B: July 2015-April 2016) remodeling. RESULTS: The IVF outcomes from 1036 cycles were associated in this study. Reduction in VOC meter readings, enhanced air quality, improvement in blastocyst formation rate, implantation, and clinical pregnancy rate were observed in the laboratory after implementation of new facilities. Results illustrated that the attention must be focused on potential hazards which expose laboratories to elevated VOC levels. Blastocyst formation rate increased around 18%. Implantation rate, clinical pregnancy rate, and live birth rate increased by around 11, 10, and 8%, respectively. CONCLUSION: In conclusion, with proper engineering and material selection, we have been able to reduce chemical contamination and adverse effects on culture with optimized IVF results. SUPPORT: None.

Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes.

BACKGROUND: Follicular fluid (FF) is an important micro-environment influencing oocyte growth, its development competence, and embryo viability. The FF content analysis allows to identify new relevant biomarkers, which could be predictive of in vitro fertilization (IVF) outcomes. Inside ovarian follicle, the amount of FF components from granulosa cells (GC) secretion, could be regulated by gonadotropins, which play a major role in follicle development. METHODS: This prospective study included 61 female undergoing IVF or Intra-cytoplasmic sperm injection (ICSI) procedure. Apolipoprotein B (APOB) concentrations in follicular fluid and APOB gene and protein expression in granulosa cells from reproductively aged women undergoing an in vitro fertilization program were measured. The statistical analyses were performed according to a quartile model based on the amount of APOB level found in FF. RESULTS: Amounts of APOB were detected in human FF samples (mean ± SD: 244.6 ± 185.9 ng/ml). The odds of obtaining an oocyte in the follicle and a fertilized oocyte increased significantly when APOB level in FF was higher than 112 ng/ml [i.e., including in Quartile Q 2, Q3 and Q4] (p = 0.001; p < 0.001, respectively). The probabilities of obtaining an embryo and a top quality embryo on day 2, were significantly higher if APOB levels were within the ranges of 112 and 330 ng/ml (i.e. in Q2 and Q3) or 112 and 230 ng/ml (i.e. in Q2), respectively (p < 0.001; p = 0.047, respectively). In addition, our experiments in vitro indicated that APOB gene and protein expression, along with APOB content into culture were significantly under-expressed in GC upon stimulation with gonadotropins (follicular stimulating hormone: FSH and/or human chorionic gonadotropin: hCG). CONCLUSION: We are reporting a positive and statistically significant associations between APOB and oocyte retrieval, oocyte fertilization, and embryo quality. Using an experimental study component, the authors report significant reduced APOB expression and content for luteinized granulosa cells cultured in the presence of gonadotropins.

The impact of follicular fluid adiponectin and ghrelin levels based on BMI on IVF outcomes in PCOS.

PURPOSE: This study aimed at evaluating the effects of polycystic ovary syndrome (PCOS) and body mass index (BMI) on follicular fluid (FF) adiponectin and ghrelin levels, and on in vitro fertilization outcomes in patients who underwent controlled ovarian hyperstimulation. METHODS: This prospective cross-sectional study was performed with a total of 120 primary infertile women [group 1; non-PCOS = 60 (BMI <25 = 30, BMI ≥25 = 30) and group 2; PCOS = 60 (BMI <25 = 30, BMI ≥25 = 30)]. On the day of oocyte pickup, FF samples were collected. RESULTS: The FF adiponectin levels were lower in the lean PCOS group than the lean non-PCOS group (p = 0.001), and these levels were lower in the overweight non-PCOS group compared to lean non-PCOS group (0.001). However, there was no difference in the FF ghrelin levels between the groups. Additionally, we could not find a relationship between clinical pregnancy and adiponectin and ghrelin levels. CONCLUSION: The FF adiponectin and ghrelin levels have no effects on clinical pregnancy in PCOS. Therefore, further studies are needed to elucidate this issue.