Changes of sFas and sFasL,oxidative stress markers in serum and follicular fluid of patients undergoing IVF

Purpose

The Fas-Fas Ligand interaction is one of the essential events for the induction of apoptosis whereas the exact role of their soluble forms in the reproductive system is still not fully understood. Also oxidative stress in the pathogenesis of infertility causing diseases in women and has been suggested as one of the important factors that negatively affect IVF outcome. In this study, our aim was to evaluate serum and follicular fluid levels of soluble Fas soluble Fas Ligand, malondialdehyde, superoxide dismutase and total antioxidant capacity in patients undergoing IVF and compared with controls.

Methods

This study included 109 patients. Patients were classified as unexplained infertility (N = 31), PCOS (N = 19), tubal factor (N = 9) and endometriosis (N = 10) and compared with male factor infertility (N = 40) that was the control group. sFas and sFasL levels were measured by immunoassay method. MDA, SOD and TAC levels were measured by colorimetric method.

Results

Patients with unexplained infertility, PCOS and tubal factor had significantly lower sFas levels compared with their controls (respectively, p < 0.01, p < 0.05, p < 0.05). However, SOD activity in unexplained infertility, PCOS and endometriosisgroupswere significantly higher than control group (p < 0.01).Decreased follicular fluid TAC levels were found in all patient groups compared with controls (respectively, p < 0.01, p < 0.05, p < 0.01, p < 0.01).Patients with tubal factor had significantly higher serum sFasL (p < 0.05), but lower follicular fluid sFasL levels (p < 0.05) compared with unexplained infertility. Tubal factor and endometriosis groups had lowerfollicular fluid TAC levels compared to unexplained infertility and PCOSgroups (p < 0.01).

Conclusion(s)

In this study, serum and follicular fluid sFas levels were decreased and antioxidant activity was impaired in infertility, possibly implying increased apoptosis. Especially in unexplained infertility group changes in this parametres more remarkable.     

Superoxide dismutase in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection

Purpose

Polycystic ovary syndrome (PCOS) is associated with oxidative stress (OS) and serum superoxide dismutase (SOD) activity has been reported with mixed results. The objective of this study was to examine the activity of SOD both in the serum and FF from women with PCOS undergoing ICSI, as well as the expression of Cu/Zn-SOD mRNA in the cells recovered from the FF.

Methods

Forty women undergoing an ICSI trial were divided into: group I, included 20 PCOS cases, group II included 20 age-matched controls with tubal factor infertility. Both groups were similarly stimulated. A total of 204 metaphase II (MII) oocytes were aspirated; (108) from PCOS, and (96) from the control group. SOD activities in the serum and FF, as well as Cu/Zn-SOD (SOD1) mRNAs in follicular fluid (FF) cells were analyzed.

Results

There was a statistically highly significant decrease (p < 0.001) both in the mean serum SOD (45.56 ± 18.06) and FF SOD activity (42.49 ± 11.46) in PCOS than the control group (77.38 ± 7.82), (74.37 ± 6.15) respectively. The mean relative levels of Cu, Zn SOD mRNAs was significantly lower (p < 0.001) in cells isolated from the FF in PCOS (0.36 ± 0.14) than the control group (0.81 ± 0.15). SOD activity in FF had no effects on fertilization rate (p > 0.05), or embryo quality after intracytoplasmic sperm injection (ICSI).

Conclusion

Although decreased SOD activity in FF has no effect on fertilization rate and/or embryo quality, serum SOD activity could be a clinical parameter for determining systemic oxidative stress in PCOS.     

Correlation between follicular diameters and flushing versus no flushing on oocyte maturity,fertilization rate and embryo quality

Objective

To determine (a) the correlation between follicular sizes, oocyte maturity, normal fertilization rate, cleavage and embryo quality; and (b) to establish whether oocytes recovered with or without follicular flushing have different developmental competence.

Design

Prospective observational study.

Setting

Academic medical center.

Patients

Forty nine cycles (37 ICSI and 12 IVF).

Interventions

Measurement of 360 follicular diameters on the day of egg retrieval and classification into three groups Group A (mean diameter 12–14.5 mm.), group B (mean diameter 15–18 mm.) and group C (diameter >18.5 mm.).

Main outcome measure

Correlation between follicular size at the time of retrieval and oocyte maturity, fertilization and cleavage rate in 226 oocytes (163 ICSI and 63 IVF). Developmental competence of oocytes retrieved with flushing versus non flushing.

Results

Almost all (99 %) of the oocytes recovered from follicles of group C were in metaphase II as opposed to 80 % in group A and 81 % in group B (p < 0.01). Overall there was a progressive and significant increase in fertilization rates from group A follicles to group C (47 % vs. 67 %, p 0.05). Overall 53 % of oocytes retrieved from group A follicles showed either no fertilization or abnormal fertilization versus 27 % in group C (p 0.05). The oocyte recovery rate with follicular flushing improved from group A to group B and to group C follicles (65 % vs. 49 % vs.37 % respectively p < 0.01). There were no differences in rates of immature oocyte, fertilization, abnormal or not fertilization and cleavage.

Conclusions

The results of this study shows that: a) Follicles larger than 18 mm at retrieval have consistently mature oocytes with a higher rate of fertilization; b) Small size follicles are still capable of containing mature oocytes, but their rate of abnormal or no fertilization is high; c) Oocytes recovered with flushing are still able to produce embryos with full developmental competence.     

Progesterone levels on the hCG day and outcomes in vitro fertilization in women with polycystic ovary syndrome

Background

The purpose of this study was to determine the incidence of premature luteinization in patients with polycystic ovary syndrome and compared the main determinants of success in in-vitro fertilization in PCOS patients with and without premature luteinization.

Methods

Retrospective analysis of 180 PCOS women of Chinese Han origin with infertility who underwent controlled ovarian hyperstimulation (COH) with an exogenous gonadotropin/GnRH antagonist protocol. Hormone levels on the hCG day and IVF outcomes were assessed.

Results

The incidence of premature luteinization was 23.3 %. Compared with PCOS patients without premature luteinization, PCOS patients with premature luteinization(PL) had a higher number of oocytes retrieved (18.20 ± 6.6 vs 15.08 ± 7.3, p = 0.037) and a higher fertilization rate (72.9 ± 1.9 vs63.1 ± 2.3, p = 0.033), but clinical pregnancy rates were no statistical significance (53.3 vs 56.0, p = 0.836). Though the implantation rate was higher in no premature luteinization patients, but the difference was not statistically significant (37.7 vs 30.3, p = 0.115).

Conclusion

The PCOS patients with premature luteinization had a higher fertilization rate and high number of oocytes retrieved, and the similar implantation rate and clinical PRs as PCOS patients without premature luteinization.     

Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems

Purpose

We aimed to analyse the in vitro fertilization-embryo transfer (IVF-ET) outcomes of the patients with sleep disturbances who were administered melatonin.

Methods

A total of 60 patients with sleep disturbances were divided into two groups. The study group (group A, n = 30) had underwent the IVF-ET with melatonin administration and the control group (group B, n = 30) without melatonin. Sleeping status after melatonin administration and the IVF outcomes were compared between the two groups.

Results

Sleeping status change was not significant (p > 0.05). The mean number of the retrieved oocytes, the mean MII oocyte counts, the G1 embryo ratio were significantly higher in the melatonin administered group (group A) than that the non-administered group (group B); p = 0.0001; p = 0.0001; p < 0.05 respectively.

Conclusion

IVF patients with sleep disorders may benefit from melatonin administration in improving the oocyte and the embryo quality, but the sleeping problem itself may not be fixed.     

Downregulation of adiponectin system in granulosa cells and low levels of HMW adiponectin in PCOS

Purpose

The purpose of the study was to investigate changes in adiponectin system expression in granulosa cells (GCs) and high molecular weight adiponectin levels in serum and follicular fluid (FF) of 40 women with polycystic ovary syndrome (PCOS) compared to those in 40 women with normal ovary function.

Methods

Adiponectin (Adipo), adiponectin receptor 1 (AdipoR1), and adiponectin receptor 2 (AdipoR2) messenger RNA (mRNA) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). High molecular weight (HMW) adiponectin protein concentration was evaluated by ELISA method. Data were analyzed using Student’s t test and one-way ANOVA in SPSS 21 software. At oocyte retrieval, FF was aspirated and GCs were obtained from a pooled collection of FF per each patient.

Results

PCR results showed expression of adiponectin, AdipoR1, AdipoR2, follicle-stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) in GCs. After controlling body mass index (BMI) values, qRT-PCR demonstrated a decreased expression of adiponectin system in GCs of PCOS patients compared to those in controls (p = 0.001). There was a strong positive correlation among AdipoR1 and AdipoR2 expression and also among FSH and LH receptor expression. (Both r = 0.8, p = 0.001). There were low levels of high molecular weight adiponectin in the serum of PCOS patients with controlled ovarian hyperstimulation (30.19 ± 4.3 ng/ml) compared to the controls (48.47 ± 5.9 ng/ml) and in the FF of PCOS patients with controlled ovarian hyperstimulation (7.86 ± 1.44 ng/ml) compared to the controls (14.22 ± 2.01 ng/ml; p = 0.02).

Conclusions

Lower expression of adiponectin and its receptors in GCs might be an important manifestation in gonadotropin-stimulated PCOS patients which could influence the physiologic adiponectin roles such as interaction with insulin and LH in induction of GC gene expression.     

Follicular fluid protein content (FSH, LH, PG4, E2 and AMH) and polar body aneuploidy

Purpose

Our objective was to identify a marker for oocyte aneuploidy in follicular fluid (FF) in women with an increased risk of oocyte aneuploidy after controlled ovarian hyperstimulation.

Materials and methods

Three groups of oocytes were constituted for polar body screening by FISH (chromosomes 13, 16, 18, 21 and 22): Group 1, advanced maternal age (n = 156); Group 2, implantation failure (i.e. no pregnancy after the transfer of more than 10 embryos; n = 101) and Group 3, implantation failure and advanced maternal age (n = 56). FSH and other proteins were assayed in the corresponding FF samples.

Results

Of the 313 oocytes assessed, 35.78 % were abnormal. We found a significant difference between the follicular FSH levels in normal oocytes and abnormal oocytes (4.85 ± 1.75 IU/L vs. 5.41 ± 2.47 IU/L, respectively; p = 0.021). We found that the greater the number of chromosomal abnormalities per oocyte (between 0 and 3), the higher the follicular FSH level.

Conclusion

High FF FSH levels were associated with oocyte aneuploidy in women having undergone controlled ovarian hyperstimulation.     

The ovarian response to standard gonadotrophin stimulation depends on FSHR, SHBG and CYP19 gene synergism

Purpose

Follicle stimulating hormone, sex hormone-binding globulin and cytochrome P450 aromatase play crucial roles in the regulation of mammalian reproduction. The synergistic effect of FSHR 307(T/A)/FSHR 680(N/S), SHBG(TAAAA)_n and CYP19(TTTA)_n genotypes on ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction (IVF/ICSI) was explored.

Methods

The study population consisted of 300 women under IVF/ICSI treatment and 300 women with at least with at least one successful child birth as controls. The polymorphisms were genotyped while the follicular size, the follicle and oocyte numbers were recorded during oocyte retrieval.

Results

The genotype analysis, excluding heterozygotes for each particular polymorphism, revealed eight combined homozygotic FSHR/SHBG/CYP19 genotypes. A gradual reduction in the number of follicles and oocytes from FSHR 307Thr/680Asn allele/long SHBG allele/long CYP19 allele homozygotes to FSHR 307Ala/680Ser allele/short SHBG allele/short CYP19 allele homozygotes was observed (20.36 ± 6.74 vs. 8.05 ± 2.47, p < 0.008 and 13 ± 4.63 vs. 6.1 ± 2.32, p < 0.02, respectively).

Conclusions

FSHR/SHBG/CYP19 combined genotypes are associated with ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction.     

Fertility management in the PCOS population: results of a web-based survey at IVF-worldwide.com

Purpose

To identify the leading treatment strategies for infertile women with PCOS on an international scale.

Methods

A retrospective evaluation using the results of a web-based survey, (IVF-Worldwide (www.IVF-worldwide.com), posted from 1 to 30 September 2010 was performed. Binomial confidence intervals for proportions were calculated by the modified Wald method with significance defined as P < 0.05 using a DataStar software package (DataStar, Waltham, MA, USA). Incomplete surveys were excluded from the analysis.

Results

The results from 262 centers in 68 nations were obtained. Clomiphene citrate was the clear first choice, 68 %, for PCOS treatment in the respondent group. Eighty-eight percent of respondents utilized ultrasound follicular monitoring when conducting ovulation induction with oral medications. A significant (p < 0.05) proportion of respondents (66 %) did use some BMI cutoff beyond which IVF treatment was not offered. The preferred IVF protocols for PCOS patients were gonadotropin releasing hormone (GnRH) antagonist, 46 %, and GnRH agonist, 51 %. There was heterogeneity of responses observed regarding the management of a patient at very high risk of OHSS.

Conclusions

While some advances, such as the use of GnRH antagonist regimen in IVF cycles, were relatively underutilized, the survey gives an unfiltered snapshot at the practice patterns of a large number of clinics. Results from this survey may be used by researchers and professional organizations to improve the clinical care of PCOS women suffering with infertility.     

Rescue in vitro fertilization using a GnRH antagonist in hyper-responders from gonadotropin intrauterine insemination (IUI) cycles

Objective

To evaluate the outcomes in the conversion of high-response gonadotropin intrauterine insemination (IUI) cycles to “rescue” in vitro fertilization (IVF) using a Gonadotropin-Releasing Hormone (GnRH) antagonist, with regards to implantation rates, pregnancy rates, cost, and ovarian hyperstimulation syndrome (OHSS) as compared to matched, hyper-responder, IVF controls.

Methods

This prospective cohort study was conducted between January 2007 and December 2009 at our institution. In order to decrease high-order multiple pregnancy, minimize the incidence of OHSS, and avoid cycle cancellation, high-response stimulated-IUI patients opted to convert to “rescue” IVF using the GnRH antagonist cetrorelix acetate. We then compared their clinical outcomes with matched patients from high-response IVF cycles of the standard long mid-luteal GnRH agonist protocol (14 or more collected oocytes). Only cases of conventional IVF without intra-cytoplasmic sperm injection (ICSI) were included in the control group.

Results

Out of 184 patients undergoing stimulated-IUI cycles with gonadotropins, 87 patients developed a hyper-response, and 20 opted to convert to “rescue” IVF. These patients were compared with 157 matched, hyper responder IVF controls from our registry. The implantation rate was 25.6 % in the “rescue” IVF group and 20.7 % in the control IVF group (p < 0.0047). The ongoing clinical pregnancy rate per embryo transfer was 45.0 % and 33.6 % in the “rescue” IVF and the control IVF groups, respectively (p < 0.0001). The mean duration of stimulation was comparable between cohorts (10.0 vs.10.4 days, p = 0.6324). The mean dose of gonadotropin used per cycle was higher in the control group, 2664 international units (IU) of follicle stimulation hormone (FSH) compared to 1450 IU of FSH in the “rescue” IVF group (p < 0.0001). The incidence of severe OHSS is also higher in the control group, 5.1 % versus no cases in the “rescue” IVF group (p < 0.0001).

Conclusion

Our study demonstrates that conversion of high-response gonadotropin-IUI cycles to “rescue” IVF using a GnRH antagonist is a cost-effective strategy that produces better results than regular IVF with relatively minimal morbidity, and shorter duration to achieve pregnancy. Implantation and ongoing clinical pregnancy rates tend to be higher than those from hyper-responder regular IVF patients.     

Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin

Purpose

The purpose of this study was to evaluate the oxidative stress status (OS) of follicular fluid (FF) and the oocyte quality in women with polycystic ovary syndrome (PCOS) undergoing different ovarian stimulation protocols.

Methods

FF samples were collected after gonadotropin administration in association or not with metformin or D-chiro-inositol (DCI). OS status was then evaluated by checking the follicular fluid protein oxidation profile after specific labeling of aminoacidic free–SH groups, and two-dimensional electrophoresis followed by qualitative and semiquantitative analysis. Oocyte quality was assessed by international morphological criteria.

Results

Our data indicated that both treatments, even if to different extent, recovered a significantly high level of free–SH groups in FF proteins of PCOS women clearly indicating a decrease of OS level with respect to that found in FF samples from gonadotropins alone treated women. A higher number of good quality MII oocytes was also observed in DCI (P < 0.05) or metformin (P < 0.05) study groups in comparison to untreated control group.

Conclusion

A natural supplement and a drug both showed a statistically significant positive effect on follicular milieu by decreasing the oxidative damage on FF proteins, as well as in recovering good quality oocytes.     

Ovarian adipocytokines are associated with early in vitro human embryo development independent of the action of ovarian insulin

Purpose

We aimed to characterize the association between levels of serum and follicular fluid (FF) adipocytokines, reflected by the leptin to adiponectin ratio (L:A ratio), and oocyte quality and in vitro embryo development in women undergoing assisted reproduction. We also aimed to assess whether follicular hormonal pathways mediate this interaction.

Methods

We prospectively collected FF from up to four individual preovulatory follicles (n = 76) and fasting sera from women (n = 31) without endocrinopathies undergoing in vitro fertilization (IVF) at a university-based center for assisted reproduction. Leptin, total adiponectin, insulin, insulin-like growth factor 1 (IGF-1), and ovarian steriods were measured using enzyme immunoassay. Oocyte maturity, fertilization, and embryo development were assessed.

Results

FF leptin was similar to serum levels while FF adiponectin was lower. FF leptin (27.10 ± 4.05 ng/mL) and the L:A ratio (11.48E−3 ± 2.57E−3) were related to FF insulin (R² = 0.370 and 0.419, p < 0.001) but not to ovarian steroids or IGF-1, whereas FF adiponectin ( 4.22 ± 0.52 ug/mL) correlated only with leptin (R² = −0.138, p = 0.001). Oocytes from a high FF L:A ratio environment were 81 % (RR 1.81 [95%CI 0.97–3.37]) more likely to undergo successful cleavage and 117 % (RR 2.17 [95 % CI 1.06–4.44]) more likely to obtain viable cleavage morphology compared to a low FF L:A ratio environment, even when adjusted for FF insulin, an independent predictor of cleavage.

Conclusions

Certain adipocytokines, particularly the L:A ratio in the FF of the preovulatory follicle, are related to successful in vitro embryo development. This action may be independent of FF insulin.     

Ovarian stimulation and in-vitro fertilization outcomes of cancer patients undergoing fertility preservation compared to age matched controls: a 17-year experience

Purpose

To compare the in-vitro fertilization (IVF) outcomes of cancer patients who underwent oocyte retrieval and embryo/oocyte cryopreservation prior to gonadotoxic therapy to those of age and time-matched controls with tubal factor infertility.

Methods

All cancer patients who underwent embryo/oocyte cryopreservation at our institution from 1997 to 2014 were reviewed. Primary outcomes were total dose of gonadotropins used, number of oocytes retrieved, and number of 2pn embryos obtained. Outcomes were compared to age-matched controls with tubal-factor infertility who underwent a fresh embryo transfer within the same relative time period as the IVF cycle of the cancer patient.

Results

Sixty-three cancer patients underwent 65 IVF cycles, and 21 returned for frozen embryo transfer. One hundred twenty-two age-matched controls underwent IVF cycles with fresh transfer, and 23 returned for frozen embryo transfer. No difference was seen between cancer patients and controls with respect to total ampules of gonadotropin used (38.0 vs. 35.6 respectively; p = 0.28), number of oocytes retrieved (12.4 vs. 10.9 respectively; p = 0.36) and number of 2pn embryos obtained (6.6 vs. 7.1 respectively; p = 0.11). Cumulative pregnancy rate per transfer for cancer patients compared to controls was 37 vs. 43 % respectively (p = 0.49) and cumulative live birth rate per transfer was 30 vs. 32 % respectively (p = 0.85). Cancer patients had a higher likelihood of live birth resulting in twins (44 vs. 14 %; p = 0.035).

Conclusions

Most IVF outcomes appear comparable for cancer patients and age-matched controls. Higher twin pregnancy rates in cancer patients may reflect lack of underlying infertility or need for cancer-specific transfer guidelines.     

Ratio of progesterone-to-number of follicles as a prognostic tool for in vitro fertilization cycles

Purpose

To establish a ratio of the P level to the number of follicles (P/F ratio) on the day of human chorionic gonadotropin (hCG) administration and to evaluate whether this ratio is associated with in vitro fertilization (IVF) outcome.

Methods

This study was conducted between January 2012 and June 2013. A total of 337 patients with cleavage-stage day-3 fresh embryo transfer with P levels ≤1.5 ng/mL on the day of hCG administration were included in the study. The main outcome was ongoing pregnancy rate.

Result(s)

The P/F ratio was calculated according to the equation (P[ng/mL]/number of follicles) on the day of final oocyte maturation. Using ROC, we established a cut-off level of 0.075 for the P/F ratio. The area under the curve (AUC) (0.756; 95 % confidence interval [CI]: 0.704–0.807) indicated that it was a good prognostic test. In group 1 (patients under 36 years old), the ongoing pregnancy rates were 57 and 30 % for patients with P/F ratios ≤ .075 and > .075, respectively, (p = 0.003). In group 2 (patients between 36 and 39 years old), the ongoing pregnancy rates were 58 % and 17 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. In group 3 (patients ≥ 40 years old), the ongoing pregnancy rates were 41.7 and 10.9 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively.

Conclusions

The P/F ratio is a good prognostic test for predicting IVF outcome that can correlate the P level with ovarian response.     

Negative effect of P72 polymorphism on p53 gene in IVF outcome in patients with repeated implantation failure and pregnancy loss

Purpose

Investigate whether R72P on p53 gene polymorphism has a higher prevalence among women with a history of recurrent implantation failure (RIF) and pregnancy loss (RPL) and its influence in their IVF cycle outcome.

Material and methods

p53 polymorphism R72P has been studied in 181 women. The control group included 83 oocyte donors. In the study group 98 women were included: 44 with RIF and 54 with RPL. From the study group, 76 patients underwent IVF-cycles (55 RPL and 21 RIF).

Results

The frequency of PP genotypes on p53 among RIF was 11.4 % compared with 18.5 % for RPL and 6 % in controls (p < 0.01). There were no significant differences with respect to patient characteristics. Significant differences were reported in pregnancy rate (69.4 % for RR/RP and 33.3 % for PP; p < 0.05), embryo implantation rate (33.3 % for RR/RP and 7.3 % for PP; p < 0.05) and ongoing pregnancy rate (53.1 % for RR/RP and 14.3 % for PP; p < 0.05) among RIF and RPL.

Conclusions

This investigation reveals that in RIF and RPL patients R72P on p53 gene is more prevalent than fertile population. Moreover, patients carrying a PP genotype on p53 codon 72 will have less chance to achieve an ongoing pregnancy. This information together with some additional markers will allow development of diagnostic tests for detects risk for RIF and RPL before infertility treatment is initiated.     

The association between androgen receptor gene CAG polymorphism and polycystic ovary syndrome: a case-control study and meta-analysis

Purpose

Many studies have been carried out to confirm the relationship between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome (PCOS), without consistent results. Hence we conducted the current study to research this relationship.

Methods

224 Chinese Han women with PCOS and 223 in vitro fertilization and embryo transplantation (IVF-ET) infertile women with tubal factor or male infertility served as the controls were recruited in our study. PCR-based assays were applied to genotype the (CAG)_n repeat alleles. A meta-analysis including 1,536 PCOS patients and 1,807 controls was conducted to produce a pooled estimate.

Results

We observed that the CAG bi-allelic mean lengths were similar in PCOS patients and controls (22.65 ± 2.5 vs. 23.09 ± 2.1, P = 0.116). When CAG bi-allelic were divided into two categories (mean repeats ≤22, >22), the short AR-CAG bi-allelic showed more frequent in PCOS group than in controls (56.25 % vs 29.14 %, P < 0.001). Further analysis presented that, in PCOS, there was a lower mean CAG repeat lengths in mean bi-allelic lengths (22.3 ± 2.5 vs. 23.9 ± 2.2, P = 0.008) and long bi-allelic lengths (24.3 ± 1.4 vs. 25.9 ± 1.6, P = 0.05) among patients with testosterone less than 0.7 ng/ml compared with those whose testosterone was more than 0.7 ng/ml. Besides, the testosterone were positively correlated with the CAG polymorphism (r = 0.237, P = 0.008), which accorded with our meta-analysis results.

Conclusions

The distribution of AR-CAG allele differed between PCOS patients and controls, and polymorphism of CAG repeat lengths may contribute to hyperandrogenism in PCOS.     

Low utilization of extra embryos in donor oocyte in vitro fertilization cycles: an ethical dilemma to donor management

Purpose

To explore outcomes of donor In Vitro Fertilization (IVF) cycles with regards to cryopreservation and utilization of extra embryos after fresh transfer.

Methods

A database search was performed to identify all consecutive fresh donor oocyte cycles from January 1, 2000 to December 31, 2010 at a private fertility laboratory. Parameters analyzed included: number of oocytes retrieved, number of patients choosing embryo cryopreservation, number of patients returning for frozen embryo transfer (FET), and pregnancy outcomes.

Results

A total of 1070 fresh oocyte donor cycles were identified. Average number of oocytes retrieved was 16.9 ± 7.9, and average number of embryos transferred was 2.3 ± 0.96. Sixty-six percent of patients cryopreserved excess embryos following fresh transfer, and only 40 % of these patients ultimately returned for FET. Patients who conceived in their fresh cycle were much less likely to return for FET than those who did not (25 % v 65 %, p < 0.001), however chance of conceiving with FET was no different between these two groups (38 % v 38 %, NS).

Conclusions

An unexpectedly low number of patients undergoing a donor oocyte IVF cycle will ultimately return to utilize extra embryos from their fresh cycle. This is concerning considering the high numbers of oocytes retrieved and the known complications from hyperstimulation, especially in light of the relatively high pregnancy rates associated with donor cycles. This raises concerns not only for donor management, but also raises ethical dilemmas when considering the large numbers of remaining embryos that will never be utilized.     

Day 3 ET,single blastocyst transfer (SBT) or frozen-thawed embryo transfer (FET): which is preferable for high responder patients in IVF/ICSI cycles?

Purpose

To compare the clinical outcomes after day 3 embryo transfer, day 5 single blastocyst transfer (SBT) and frozen-thawed embryo transfer (FET) in high responder patients (>15 retrieved oocytes) undergoing IVF/ICSI treatment.

Methods

A retrospective analysis of three embryo transfer strategies for the high responder patients in IVF/ICSI cycles. The 1041 high responder patients diagnosed as primary infertility with more than 15 oocytes retrieved were recruited in Day 3 ET group, 308 patients with more than 15 oocytes retrieved first transferred with one blastocyst in SBT group and 425 patients with more than 15 oocytes retrieved in fresh cycle, first transferred with one frozen-thawed blastocyst were assigned in FET group.

Results

In the high responder patients, the clinical pregnancy rate after day 5 SBT was significantly lower than that of day 3 ET (43.18 % VS 57.16 %, p < 0.05). In addition, the clinical pregnant rate and implantation rate of FET cycles were significantly higher than SBT cycles (59.06 % vs. 43.18 % and 64.70 % vs. 47.40 %, p < 0.05). The multiple pregnancy rate in FET cycles was markedly lower than that of day 3 ET (2.35 % VS 34.97 %, p < 0.05).

Conclusions

FET was the preferable strategy for the high responder patients in IVF/ICSI cycles to obtain both desirable clinical outcome and lower multiple pregnancy rates.     

What is the optimal threshold of serum Anti-Müllerian hormone (AMH) necessary for IVM treatments?

Purpose

To assesse circulating levels of Anti-Müllerian hormone (AMH) as a predictor of oocyte number and their potential to mature in vitro in both normo-ovulatory (NO) women and in women with Polycystic Ovary Syndrome (PCOS) undergoing in vitro maturation (IVM) treatments.

Methods

We prospectively studied NO women and women diagnosed with PCOS, (age range 21–39 years) underwent IVM treatments at our center. Serum AMH levels were quantified before each cycle and correlated to oocytes number, maturation and fertilization during in vitro maturation.

Results

104 NO and 30 PCOS IVM cycles were followed with retrieval of a total of 672 and 491 oocytes, respectively. In NO women, the serum AMH level positively correlated with the number of oocytes retrieved, (R = 0.6; P <0.0001) the number of M2 oocytes at 24 and 48 h (R = 0.4; P <0.01; R = 0.26 p < 0.007, respectively) and with the total number of M2 oocytes (R = 0.47; P < 0.0001). In the PCOS group, the serum AMH level positively correlated only with the number of oocytes retrieved (R = 0.43; P <0.03). Receiver operating characteristic (ROC) analyses showed that a cutoff AMH level of 1.56 (ng/ml) could identify patients with 5 or more oocytes at OPU with a sensitivity of 83 % and a specificity of 75 %. An AMH level of 1.63 (ng/ml) was the threshold for 5 or more matured oocytes (sensitivity = 81 %, specificity = 53 %).

Conclusions

Serum AMH may be used as a marker to identify candidates for IVM treatment in both NO and PCOS women.