Perifollicular blood flow and its relationship with endometrial vascularity,follicular fluid EG-VEGF,IGF-1, and inhibin-a levels and IVF outcomes

Purpose

The aim of this study is to investigate the association of perifollicular blood flow (PFBF) with follicular fluid EG-VEGF, inhibin-a, and insulin-like growth factor-1 (IGF-1) concentrations, endometrial vascularity, and IVF outcomes.

Methods

Forty women with tubal factor infertility were included in a prospective cohort study. Each woman underwent IVF/ICSI procedure. Individual follicles of ≥16 mm (n?=?156) were evaluated by power Doppler analysis and categorized as well-vascularized follicles (WVFs) or poorly vascularized follicles (PVFs). WVFs referred to those with perifollicular vascularity of 51–100 %. Each follicular fluid (FF) was individually aspirated and FF/serum EG-VEGF, inhibin-a, and FF IGF-1 levels were evaluated. Zones III–IV endometrial vascularity was classified as a well-vascularized endometrium (WVE). The presence of a WVE and mature oocytes, in addition to the embryo quality and clinical pregnancy rate (CPR), were recorded for each follicle. The main outcome measures were FF serum EG-VEGF, inhibin-a, IGF-1 levels, and WVE and IVF outcome per PFBF.

Results

For WVFs, the level of FF EG-VEGF (p?=?0.008), oocyte quality (p?=?0.001), embryo quality (p?=?0.002), a WVE (p?=?0.001), and CPR (p?=?0.04) increased significantly. The pregnant group was characterized by increased numbers of WVFs (p?=?0.044), a WVE (p?=?0.022), and increased levels of FF IGF-1 (p?=?0.001) and serum EG-VEGF (p?=?0.03). FF IGF-1 >50 ng/mL (AUC 0.72) had 75 % sensitivity and 64 % specificity for predicting CPR.

Conclusions

WVFs yield high-quality oocytes and embryos, a WVE, increased FF EG-VEGF levels, and increased CPRs.

     

Anti-Müllerian hormone is produced heterogeneously in primate preantral follicles and is a potential biomarker for follicle growth and oocyte maturation in vitro

Purpose

The main goals of this study were to investigate the expression of anti-Müllerian hormone (AMH) and its receptor (AMHR2) during follicular development in primates, and to evaluate the potential of AMH as a biomarker for follicle growth and oocyte maturation in vitro.

Methods

The mRNA and protein expression of AMH and AMHR2 were determined using isolated follicles and ovarian sections from rhesus macaques (n?=?4) by real-time PCR and immunohistochemistry, respectively. Isolated secondary follicles were cultured individually. Follicle growth and media AMH concentrations were assessed by ELISA. The mRNA expression profiles, obtained from RNA sequencing, of in vitro- and in vivo-developed antral follicles were compared. Secondary follicles from additional animals (n?=?35) were cultured. Follicle growth, oocyte maturation, and media AMH concentrations were evaluated for forecasting follicular development in vitro by AMH levels.

Results

AMH immunostaining was heterogeneous in the population of preantral follicles that were also stained for AMHR2. The mRNA expression profiles were comparable between in vivo- and in vitro-developed follicles. AMH levels produced by growing follicles were higher than those of nongrowing follicles in culture. With a cutoff value of 1.40 ng/ml, 85 % of nongrowing follicles could be identified while eliminating only 5 % of growing follicles. Growing follicles that generated metaphase II-stage oocytes secreted greater amounts of AMH than did those yielding immature germinal vesicle-stage oocytes.

Conclusions

AMH, co-expressed with AMHR2, was produced heterogeneously by preantral follicles in macaques with levels correlated positively with follicle growth and oocyte maturation. AMH may serve as a biomarker for primate follicular development in vitro.

     

Anti Müllerian Hormone (AMH) level and expression in mural and cumulus cells in relation to age

Background

Serum AMH is declining with age and is highly associated with ovarian follicular reserve and disordered folliculogenesis. However, the precise role of AMH in the process of human follicular aging has still to be determined.

Aim

This study investigates AMH level in the follicular fluid (FF) and mRNA expression pattern in cumulus and mural granulosa cells of human ovarian follicles in relation to age.

Methods

We conducted a prospective study. Sixty-eight women undergoing In vitro fertilization (IVF) treatment were enrolled in the study. We obtained FF, mural and cumulus granulosa cells from large preovulatory follicles (17-20 mm) of 21–35 years old women (n?=?40) and 40–45 years old women (n?=?28) during oocyte pickup.

Results

Higher level of AMH mRNA expression in cumulus cells was observed in the older age group compared to the younger (P <0.01). In accordance with AMH mRNA expression results, FF AMH protein levels were significantly higher in the older group than in the younger group (4.7?±?1.1 ng\ml and 2.3?±?0.2 ng\ml respectively, p?<?0.002).

Conclusions

AMH is highly expressed and secreted from cumulus GCs of advanced age patients. This remarkable correlation between AMH mRNA levels in cumulus cells in respect to age suggests that AMH may be involved in follicular aging process.

     

Interleukin 15 concentrations in follicular fluid and their effect on oocyte maturation in subfertile women undergoing intracytoplasmic sperm injection

Purpose

To calculate the concentrations of interleukin 15 (IL-15) in follicular fluid (FF) and evaluate their relation with oocyte maturation, follicle size, and patients’ body mass index (BMI) and age.

Methods

Follicular fluid specimens were obtained from 56 subfertile women undergoing intracytoplasmic sperm injection (ICSI) during oocyte retrieval for measurement of IL-15 concentrations with ELISA. Wilcoxon’s test and Pearson’s correlation coefficient were used to correlate FF concentrations of IL-15 with follicular size and stage of oocyte maturation, along with patients’ BMI and age.

Results

IL-15 concentrations in FF of follicles with immature oocytes were significantly greater than those from follicles with mature ones (median 5.333 vs. 3.250 pg/ml, respectively, p?<?0.001). There was a significant negative correlation between IL-15 concentrations and follicle size (r?=???0.333, p?=?0.003). No significant correlation was observed between IL-15 concentrations and patients’ BMI and age (p?>?0.05).

Conclusions

IL-15 concentrations in FF are adversely related with the size of the follicles and the maturity of the corresponding retrieved oocytes in a cohort of expected normal responders undergoing intracytoplasmic sperm injection (ICSI). Follicular fluid concentrations of IL-15 should be investigated as a possible predictive factor for oocyte maturity.

     

IVF results in patients with very low serum AMH are significantly affected by chronological age

Purpose

The aims of this study were to assess the outcome of in vitro fertilization (IVF) in women with very low circulating anti-müllerian hormone (AMH) and to investigate factors affecting their probability of pregnancy.

Methods

The outcome of 448 IVF cycles in 361 women with circulating AMH <0.5 ng/ml was retrospectively analyzed.

Results

Cycle cancellation rate was 14.5 %; patients whose cycle was cancelled had significantly lower AMH than women who reached oocyte pickup (OPU). Among those who reached OPU, age significantly affected the success rate: despite comparable AMH levels, patients below 35 years obtained significantly more oocytes and a better clinical pregnancy rate (CPR)/OPU than patients aged 35–39 or 40–43 (31 % vs. 23.2 % vs. 10.2 %, respectively; p?=?0.001). Differently, comparable IVF results were observed stratifying patients for AMH levels in the range 0.14–0.49 ng/ml. Multivariable logistic regression analysis confirmed that the probability of pregnancy was significantly affected by age, but not by small differences in AMH level.

Conclusions

Women with very low (<0.5 ng/ml) AMH levels undergoing IVF still have reasonable chances of achieving a pregnancy, but their prognosis is significantly affected by chronological age. Very low AMH levels are associated with a relevant risk of cycle cancellation but should not be considered a reason to exclude a couple from IVF.

     

The association between fatty acid index and in vitro fertilization outcomes

Purpose

Fatty acids have been shown to play an important role in oocyte competence and early implantation of the embryo. Our hypothesis-generating study sought to determine if individual fatty acids expressed as a percentage of total erythrocyte fatty acids are associated with embryo quality and other in vitro fertilization (IVF) outcomes.

Methods

This was a prospective cohort study at an academic fertility center. Sixty women undergoing their first IVF cycle were recruited. Serum measurements of 22 fatty acids were obtained. We calculated each fatty acid as a percentage of total fatty acids, defined as the index for that individual fatty acid.

Results

Omega-3 index had no correlation with IVF outcomes. A negative correlation was found between the trans fatty acid index, elaidic acid (EA), and IVF outcomes, including fertilization rate (r = ? 0.261, p = 0.04), blastocyst conversion rate (r = ? 0.41, p = 0.001), and number of usable blastocysts and embryos (r = ? 0.411, p = 0.001). There was no correlation between EA index and number of oocytes retrieved, embryo grade, or clinical pregnancy. No consistent correlations were observed with the additional fatty acids analyzed.

Conclusions

No correlation was observed between omega-3 index and IVF outcomes. Elevated erythrocyte EA index, the major trans fatty acid commonly consumed in hydrogenated oils, margarine, and fried foods, was negatively correlated with number of usable blastocysts and embryos, blastocyst conversion, and fertilization rate. Our findings suggest preliminary evidence that trans fat may be negatively associated with IVF outcomes.

     

Effects of salpingectomy during abdominal hysterectomy on ovarian reserve: a randomized controlled trial

Background

The aim of this study was to investigate the effect of salpingectomy on ovarian function by measuring AMH.

Methods

This study was a balanced, single-center, double-blind, randomized, controlled trial in Ruin Tan Arash Hospital, Tehran, between May 2013 and November 2014. A total of 30 patients undergoing elective abdominal hysterectomy were randomized into two groups, 15 with salpingectomy and 15 without salpingectomy. The primary objective of this study was to compare mean difference of anti-Mullerian hormone (AMH) between two groups. The secondary outcomes measured were follicle-stimulating hormone (FSH), operative time, and blood loss.

Results

Serum AMH levels decreased at 3 months after hysterectomy in all patients (pre AMH 1.32 ± (0.91); post AMH 1.05 ± (0.88), P < 0.001), the salpingectomy group (pre AMH 1.44 ± (0.94); post AMH 1.13 ± (0.86), P < 0.001), and no salpingectomy group (pre AMH 1.2 ± (0.9); post AMH 0.97 ± (0.92), P < 0.001). The rate of decline of AMH levels after surgery did not differ between the two groups (25% (17–33%) vs. 26% (15–36%), P = 0.23) among the women with salpingectomy versus without salpingectomy, respectively. There was no difference in the mean operative time (mean difference 0.33, 95% CI ??22.21 to 22.86, P < 0.92), mean blood loss (mean difference ??0.66, 95% CI ??15.8 to 14.46, P < 0.97), and post FSH (mean difference 0.34, 95% CI ??1.2 to 1.88, P < 0.65) between both groups.

Conclusions

Salpingectomy with abdominal hysterectomy is a safe treatment that does not have a deleterious effect on ovarian reserve.

Trial registration

Iranian Registry of Clinical Trials, IRCT2014123118866N4 (www.IRCT.ir)

     

Decreased live births among women of Middle Eastern/North African ethnicity compared to Caucasian women

Purpose

The objective of this study is to determine if IVF outcome disparities exist among MENA women in the USA in comparison to a control group of Caucasian women.

Methods

A retrospective cohort study comparing MENA (N = 190) and Caucasian (N = 200) women undergoing their first IVF cycle between 5/2006 and 5/2014 was carried out at an academically affiliated fertility practice. All MENA cycles during that time period undergoing IVF/ICSI using autologous embryos and blastocyst transfers were compared to a control group of Caucasian women.

Results

MENA women were significantly younger (32.9 vs 34.5, P < 0.005) and had a lower BMI (25.2 vs 27.1, P < 0.001). Male factor infertility was higher among partners of MENA women (62 vs 50%, P < 0.05). MENA women experienced decreased live birth rates per blastocyst transfer compared to Caucasian women after controlling for age and BMI (OR 0.55, 95% CI 0.35–0.85 P = 0.007). The odds of a miscarriage were also significantly higher among MENA women (OR 2.55, 95% CI 1.04–6.27 P = 0.036).

Conclusion

Middle Eastern/North African women have worse IVF outcomes with decreased live birth rates per blastocyst transfer and increased miscarriage rates compared to Caucasian women.

     

Vitamin D as a follicular marker of human oocyte quality and a serum marker of in vitro fertilization outcome

Purpose

This study investigated the relationship between the vitamin D [25(OH)D] level in individual follicles and oocyte developmental competence.

Methods

A prospective cohort study in a private infertility center. Infertile women (N?=?198) scheduled for intracytoplasmic sperm injection (ICSI) and a single embryo transfer (SET) provided serum samples and 322 follicular fluid (FF) specimens, each from a single follicle on the day of oocyte retrieval.

Results

FFs corresponding to successfully fertilized oocytes (following ICSI) contained significantly lower 25(OH)D level compared with those that were not fertilized (28.4 vs. 34.0 ng/ml, P?=?0.001). Top quality embryos on the third day after fertilization, when compared to other available embryos, developed from oocytes collected from follicles containing significantly lower 25(OH)D levels (24.56 vs. 29.59 ng/ml, P?=?0.007). Positive hCG, clinical pregnancy, and live birth rates were achieved from embryos derived from oocytes that grew in FF with significantly lower 25(OH)D levels than in follicles not associated with subsequent pregnancy. The concentration of 25(OH)D in FF in women with negative hCG was 32.23?±?20.21 ng/ml, positive hCG 23.62?±?6.09 ng/ml, clinical pregnancy 23.13?±?6.09 ng/ml, and live birth 23.45?±?6.11 ng/ml (P?<?0.001). Women with serum 25(OH)D?<?20 ng/ml had not only a higher fertilization rate (71 vs. 61.6%, P?=?0.026) and a higher clinical pregnancy rate (48.2 vs. 25%, P?=?0.001), but also higher miscarriage rate (14.5 vs. 3.8%, P?=?0.013) compared with those with levels ≥?20 ng/ml.

Conclusion

This study reveals that the level of 25(OH)D in FF correlates negatively with the oocytes’ ability to undergo fertilization and subsequent preimplantation embryo development. Oocytes matured in FF with low 25(OH)D concentration are more likely to produce top quality embryos and are associated with higher pregnancy and delivery rates. On the other hand, low serum vitamin D concentration is associated with higher miscarriage rates.

     

Differential response of AMH to GnRH agonist among individuals: the effect on ovarian stimulation outcomes

Purpose

The purpose of this study is to investigate whether individual response of anti-Mullerian hormone (AMH) to gonadotropin-releasing hormone (GnRH) treatment is associated with difference in ovarian stimulation outcomes.

Methods

The retrospective study included 1058 non-polycystic ovary syndrome (PCOS) women undergoing long agonist protocol in a single in vitro fertilization unit from January 1, 2016, through December 31, 2016. Patients were grouped according to AMH changes from day 3 to the day of stimulation (group 1, change <?1 ng/ml, n?=?714; group 2, decrease ≥?1 ng/ml, n?=?143; group 3, increase ≥?1 ng/ml, n?=?201). A generalized linear model including Poisson distribution and log link function was used to evaluate the association between AMH response and the number of oocytes retrieved.

Results

Group 2 was characterized by higher basal AMH level and increased AMH to AFC ratio in comparison with two other groups. However, the number of oocytes and ovarian sensitivity index in group 2 was significantly lower than group 3. Adjusted for age, BMI, ovarian reserve markers, and stimulation parameters, the population marginal means (95% confidence interval) of oocyte number in groups 1 through 3 were 9.51 (9.17, 9.86), 8.04 (7.54, 8.58), and 10.65 (10.15, 11.18), respectively. For patients from group 2 and group 3, basal AMH is no longer significantly associated with oocyte yield.

Conclusions

AMH change in response to GnRH agonist varies among individuals; for those undergoing significant changes in AMH following GnRH agonist treatment, basal AMH may not be a reliable marker for ovarian response in long agonist protocol.

     

Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage?

Purpose

We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage.

Methods

Twenty-four adult female Sprague–Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH-positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed.

Result(s)

The mean serum AMH concentrations were 1.3?±?0.19, 0.16?±?0.03, and 0.27?±?0.20 ng/mL in groups 1, 2, and 3, respectively (p?<?0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p?<?0.01 and p?=?0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p?<?0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p?=?0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p?<?0.01, p?<?0.01, and p?<?0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p?<?0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p?<?0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p?=?0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p?=?0.03).

Conclusion(s)

CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known.

     

Extracellular microRNAs in follicular fluid and their potential association with oocyte fertilization and embryo quality: an exploratory study

Purpose

The purpose of this study is to determine the profile of extracellular microRNAs (exmiRNAs) in follicular fluid (FF) and explore their association with fertilization potential and embryo quality.

Methods

We collected FF from single follicles containing mature oocytes from 40 women undergoing IVF and we screened for the expression of 754 exmiRNAs in FF using the TaqMan OpenArray® qPCR platform. To determine the association of exmiRNAs and IVF outcomes, we compared their expression levels in FF samples that differ by fertilization status (normally, abnormally, and failed to fertilize) and embryo quality (top vs. non-top).

Results

We detected 207 exmiRNAs, of which miR-30d-5p, miR-320b, miR-10b-3p, miR-1291, and miR-720 were most prevalent. We identified four exmiRNAs with significant fold change (FC) when FF that contained normally fertilized was compared to failed to fertilize oocytes [miR-202-5p (FC?=?1.82, p?=?0.01), miR-206 (FC?=?2.09, p?=?0.04), miR-16-1-3p (FC?=?1.88, p?=?0.05), and miR-1244 (FC?=?2.72, p?=?0.05)]. We also found four exmiRNAs to be significantly differentially expressed in FF that yielded top quality versus non-top quality embryos [(miR-766-3p (FC?=?1.95, p?=?0.01), miR-663b (FC?=?0.18, p?=?0.02), miR-132-3p (FC?=?2.45, p?=?0.05), and miR-16-5p (FC?=?3.80, p?=?0.05)]. In-silico analysis revealed that several of these exmiRNAs are involved in pathways implicated in reproductive system diseases, organismal abnormalities, and organ development.

Conclusions

Our findings suggest that exmiRNAs in the follicular fluid can lead to downstream events that will affect fertilization and day 3 embryo morphology. We encourage further observational and experimental studies to confirm our findings and to determine the role of exmiRNAs in human reproduction.

     

Comparing blastocyst quality and live birth rates of intravaginal culture using INVOcell™ to traditional in vitro incubation in a randomized open-label prospective controlled trial

Purpose

The purpose of this study is to to compare the efficacy of intravaginal culture (IVC) of embryos in INVOcell? (INVO Bioscience, MA, USA) to traditional in vitro fertilization (IVF) incubators in a laboratory setting using a mild pre-determined stimulation regimen based solely on anti-mullerian hormone (AMH) and body weight with minimal ultrasound monitoring. The primary endpoint examined was total quality blastocysts expressed as a percentage of total oocytes placed in incubation. Secondary endpoints included percentage of quality blastocysts transferred, pregnancy, and live birth rates.

Methods

In this prospective randomized open-label controlled single-center study, 40 women aged <38 years of age with a body mass index (BMI) of <36 and an AMH of 1–3 ng/mL were randomized prior to trigger to receive either IVC or IVF. Controlled ovarian stimulation was administered with human menopausal gonadotropin (hMG) in a fixed gonadotropin-releasing hormone (GnRH) agonist cycle based solely on AMH and body weight. A single ultrasound-monitoring visit was performed on the 10th day of stimulation. One or two embryos were transferred following 5 days of culture.

Results

IVF produced a greater percentage of total quality embryos as compared to IVC (50.6 vs. 30.7 %, p?=?0.0007, respectively). There was no significant difference between in IVF and IVC in the percentage of quality blastocysts transferred (97.5 vs. 84.9 %, p?=?0.09) or live birth rate (60 % IVF, 55 % IVC).

Conclusions

IVF was shown to be superior to IVC in creating quality blastocysts. However, both IVF and IVC produced identical blastocysts for transfer resulting in similar live birth rates. IVC using INVOcell? is effective and may broaden access to fertility care in selected patient populations by ameliorating the need for a traditional IVF laboratory setting. Further studies will help elucidate the potential physiological, psychological, geographic, and financial impact of IVC on the delivery of fertility care.

     

Follicular growth after xenotransplantation of cryopreserved/thawed human ovarian tissue in SCID mice: dynamics and molecular aspects

Purpose

To study the influence of xenotransplantation on follicular recruitment and growth in cryopreserved/thawed human ovarian tissue.

Method

Two 3-mm pieces of cryopreserved/thawed human ovarian tissue obtained from female cancer patients (n?=?11) were xenotransplanted into a subcutaneous neck pouch of 6-week-old ovarectomized SCID mice (n?=?33) for 4 (n?=?18) and 12 (n?=?15) weeks.

Result

Thirty-two out of 33 mice survived the entire observation periods. Graft recovery rate was 95.58 % (65 of 68 grafts). The percentages of primordial follicles after 4 weeks (P?<?0.001) and 12 weeks (P?=?0.009) of grafting were significantly lower in comparison to pregraft controls. The percentage of secondary follicle was significantly higher after 4 weeks of grafting (P?=?0.018) and after 12 weeks (P?=?0.001) of grafting in comparison to pregraft controls. Ki67 immunohistochemistry showed that proliferative follicles were significantly higher after 4 and 12 weeks of grafting compared to pregraft controls (P?<?0.001). All follicles analyzed by TUNEL staining appeared healthy after xenotransplantation. The expression level of PTEN was reduced by 2.47-fold after 4 weeks of xenotransplantation, and this result was significant when 2^?ΔCt were analyzed (P?=?0.042).

Conclusion

The higher proportion of growing follicles compared to resting follicles observed after xenotransplantation is most likely due to downregulation of PTEN gene expression followed by acceleration of follicular recruitment.

     

The cost of a euploid embryo identified from preimplantation genetic testing for aneuploidy (PGT-A): a counseling tool

Purpose

To determine the expected out-of-pocket costs of IVF with preimplantation genetic testing for aneuploidy (PGT-A) to attain a 50%, 75%, or 90% likelihood of a euploid blastocyst based on individual age and AMH, and develop a personalized counseling tool.

Methods

A cost analysis was performed and a counseling tool was developed using retrospective data from IVF cycles intended for PGT or blastocyst freeze-all between January 1, 2014 and August 31, 2017 (n?=?330) and aggregate statistics on euploidy rates of >?149,000 embryos from CooperGenomics. Poisson regression was used to determine the number of biopsiable blastocysts obtained per cycle, based on age and AMH. The expected costs of attaining a 50%, 75%, and 90% likelihood of a euploid blastocyst were determined via 10,000 Monte Carlo simulations for each age and AMH combination, incorporating age-based euploidy rates and IVF/PGT-A cost assumptions.

Results

The cost to attain a 50% likelihood of a euploid blastocyst ranges from approximately $15,000 U.S. dollars (USD) for younger women with higher AMH values (≥?2 ng/mL) to >?$150,000 for the oldest women (44 years) with the lowest AMH values (<?0.1 ng/mL) in this cohort. The cost to attain a 75% versus 90% likelihood of a euploid blastocyst is similar (~?$16,000) for younger women with higher AMH values, but varies for the oldest women with low AMH values (~?$280,000 and >?$450,000, respectively). A typical patient (36–37 years, AMH 2.5 ng/mL) should expect to spend ~?$30,000 for a 90% likelihood of attaining a euploid embryo.

Conclusions

This tool can serve as a counseling adjunct by providing individualized cost information for patients regarding PGT-A.

     

Follicular ADAMTS-1 and aggrecan levels in polycystic ovary syndrome

Purpose

Polycystic ovary syndrome (PCOS) is the most common cause of ovulatory dysfunction and female infertility. The etiopathogenetic mechanisms of PCOS have been studied for many years, although exact causes remain unclear. It has been demonstrated that proteoglycan degradation by a disintegrin-like metalloproteinase with thrombospondin type motifs-1 (ADAMTS-1) is essential for ovulation and fertilization. The objective of our study is to analyze the levels of ADAMTS-1 and aggrecan in the follicular fluid (FF) of PCOS patients compared with normal ovulatory women and to determine whether these markers could be a predictor of in vitro fertilization (IVF) success in PCOS patients.

Methods

Women with PCOS (n = 21) and normal ovulatory controls (n = 22) undergoing IVF treatment were recruited. ADAMTS-1 and aggrecan levels were analyzed with enzyme-linked immunosorbent assay (ELISA) and compared between PCOS and normal ovulatory controls. The predictor effect of ADAMTS-1 and aggrecan on fertilization rate and implantation was evaluated.

Results

FF ADAMTS-1 and aggrecan levels increased in women with PCOS compared to controls. Elevated ADAMTS-1 levels but not aggrecan were related to increased implantation in PCOS.

Conclusion

Our study demonstrated that altered levels of ADAMTS-1 and aggrecan may have a partial role in the etiopathogenesis of PCOS, and ADAMTS-1 could be a predictive marker for implantation success in PCOS patients.

     

Ovarian environment aging: follicular fluid lipidomic and related metabolic pathways

Purpose

The decline in female fecundity with age may be caused by decreased oocyte quality, a factor that may be associated with the altered composition of follicular fluid (FF).

Methods

In an effort to better understand follicular aging and the role of lipids in a given biological system, we present a prospective study that compares lipid profiles of FF from women older than 35 years (aging group, n?=?12) to women equal or younger than 35 years old (control group, n?=?17). FF lipids were extracted, and mass spectra were generated using a Waters Synapt G1 Q-TOF in MS mode. MS data was evaluated for both multi- and univariate statistics. The lipids identified as potential biomarkers of follicle aging were attributed by the online databases Lipid Maps, followed by pathway network analysis using Cytoscape software.

Results

The in vitro fertilization (IVF) parameters showed significant differences in aging, number of follicles, total number of oocytes and oocytes in MII, and number of injected oocytes. Additionally, FF from the aging group revealed 11 lipids with higher abundance, while FF from the control group included 4 lipids with higher abundance.

Conclusions

We suspect that aging may influence lipid metabolism in a downstream cascade leading, ultimately, to decreased oocyte quality. The discovery of target lipids may assist oocyte selection for IVF in the future. Furthermore, systems biology approach based on post-genomic medicine may help unravel a number of altered mechanisms not previously understood.

     

The effect of follicle size and homogeneity of follicular development on the morphokinetics of human embryos

Purpose

Our aim was to investigate follicular size (large, ≥17 mm and small, <17 mm) at the time of OPU and homogeneity of follicular development (homogenous development: follicles being present in a homogenous spread of all sizes; heterogeneous: a predominance of small and large follicles) by analysing the morphokinetics of embryo development.

Methods

In this prospective cohort study, 2526 COCs belonging to 187 patients were cultured to day 5. Embryos were evaluated morphokinetically. Four subgroups were defined: large follicles from heterogeneous cycles (LHet) and homogenous cycles (LHom) and small follicles from heterogeneous cycles (SHet) and homogenous cycles (SHom).

Results

Rates of fertilization, blastocyst formation and top and good quality blastocysts were found to be significantly higher in embryos from the LHom group (p < 0.001; p < 0.001; p < 0.001). Small follicles from both homogenous and heterogeneous cycles had significantly lower blastocyst formation and top and good quality blastocyst rates (p < 0.001; p < 0.001). Embryos from SHet had significantly more direct cleavages (p = 0.011). Time to reach blastocyst was shorter in SHom than LHet and LHom (p = 0.002; p = 0.027, respectively). However, once the blastocyst stage was achieved, implantation rates were not significantly different between subgroups, the highest rate being observed in the LHom group. Multivariable analysis revealed that homogeneity of follicular development and follicular size had a significant effect on blastocyst development and quality (p = 0.049; p < 0.001, respectively).

Conclusion

Follicular dynamics, illustrated by follicular size and homogeneity of follicular development, influence early human embryo development. Patterns of follicular growth have an impact on embryo quality and viability which is reflected in morphokinetic variables.

     

Electronic witness system in IVF—patients perspective

Objective

The objective of this study is to evaluate patient concerns about in vitro fertilization (IVF) errors and electronic witness systems (EWS) satisfaction.

Design

The design of this study is a prospective single-center cohort study.

Setting

The setting of this study was located in the private IVF center.

Patient(s)

Four hundred eight infertile patients attending an IVF cycle at a GENERA center in Italy were equipped with an EWS.

Intervention(s)

Although generally recognized as a very rare event in IVF, biological sample mix-up has been reported in the literature. For this reason, some IVF laboratories have introduced EWS with the aim to further reduce the risk of error during biological samples handling. Participating patients received a questionnaire developed through a Likert scale ranging from 1 to 6.

Main outcomes measure(s)

Patient concerns about sample mix-up without and with an EWS were assessed.

Result(s)

90.4 % of patients expressed significant concerns relating to sample mix-up. The EWS reduced these concerns in 92.1 % of patients, 97.1 % of which were particularly satisfied with the electronic traceability of their gametes and embryos in the IVF laboratory. 97.1 % of patients felt highly comfortable with an IVF center equipped with an EWS. Female patients had a significantly higher appreciation of the EWS when compared to their male partners (p?=?0.029). A significant mix-up event occurred in an Italian hospital during the study and patient’s satisfaction increased significantly towards the use of the EWS after the event (p?=?0.032).

Conclusion(s)

EWS, by sensibly reducing the risk for sample mix-up in IVF cycles, has been proved to be a trusted strategy from patient’s perspective.