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.

     

Agonist depot versus OCP programming of frozen embryo transfer: a retrospective analysis of freeze-all cycles

Purpose

In segmented ART treatment or so-called ‘freeze-all’ strategy fresh embryo transfer is deferred, embryos cryopreserved, and the embryo transferred in a subsequent frozen embryo transfer (FET) cycle. The purpose of this cohort study was to compare a GnRHa depot with an oral contraceptive pill (OCP) programming protocol for the scheduling of an artificial cycle FET (AC-FET) after oocyte pick-up (OPU).

Methods

This retrospective cohort study was conducted on prospectively performed segmented ART cycles performed between September 2014 and April 2015. The pregnancy, treatment duration, and cycle cancellation outcomes of 170 OCP programmed AC-FET cycles were compared with 241 GnRHa depot programmed AC-FET cycles.

Results

No significant difference was observed in the per transfer pregnancy and clinical pregnancy rates between the OCP and GnRHa groups, 72.0 versus 77.2 %, and 57.8 versus 64.3 %, respectively. Furthermore, the early pregnancy loss rate was non-significantly different between the OCP and GnRH protocol groups, 19.8 versus 16.7 %, respectively. However, nine (5.29 %) cycles were cancelled due to high progesterone in the OCP protocol group, while no cycles were cancelled in the GnRHa protocol group and the time taken between OPU and FET was 19 days longer (54.7 vs 35.6 days) in the OCP protocol compared to the GnRHa protocol.

Conclusions

The results of this AC-FET programming study suggests that the inclusion of GnRHa depot cycle programming into a segmented ART treatment will ensure pregnancy, while significantly reducing treatment duration and cycle cancellation.

     

Role of AMH as Diagnostic Tool for Polycystic Ovarian Syndrome

Background

To evaluate role of AMH as a diagnostic tool for PCOS.

Methods

This was a prospective case–control study on women attending Gynae OPD of Dr RML Hospital, New Delhi, from 1 November 2015 to 31 March 2017. Study comprised of 45 women with PCOS, diagnosed using Rotterdam criteria and 45 women as controls. Clinical history included oligomenorrhea, hirsutism, examination included BMI, Ferriman–Gallwey score, investigations included blood for FSH, LH, estradiol, TSH, prolactin, total testosterone, AMH level and pelvic USG which was done for all women.

Results

Both PCOS cases and control were matched for age and BMI. Median AMH levels of 4.32 ng/ml in PCOS cases was almost twice that of 2.32 ng/ml in controls (p = 0.001). Maximum diagnostic potential of AMH alone for PCOS was at a cut-off of 3.44 ng/ml with sensitivity of 77.78% and specificity of 68.89%. AMH was used as an adjunct to existing Rotterdam criteria as the fourth parameter OA+HA+PCOM+AMH (any three out of four) yielded sensitivity of 80%. However, when PCOM in Rotterdam criteria was replaced by AMH, OA+HA+AMH (any two out of three) or OA/HA+AMH resulted in sensitivity of 86.67 and 71.11%, respectively.

Conclusion

AMH levels were significantly higher in PCOS than in controls. AMH as an independent marker could not effectively diagnose PCOS. However, AMH levels as an adjunct to existing Rotterdam criteria for diagnosis of PCOS had good diagnostic potential.

     

Anti-Mullerian hormone concentrations in individual follicular fluids within one stimulated IVF cycle resemble blood serum values

Purpose

Anti-Mullerian hormone (AMH) is commonly known as the most potent marker for ovarian reserve due to its decline as female age increases. While serum AMH (sAMH) levels have been intensively investigated, there is less data regarding AMH concentrations in follicular fluid (FF), since FF has usually been designated as waste product during oocyte collection in assisted reproductive technologies. This pilot study investigated follicle AMH concentrations (fAMH) of several follicles per ovary, individually collected with the Steiner-Tan needle, and compared them to sAMH concentrations in women undergoing IVF treatment. We hypothesized that there is no difference of fAMH concentrations in individual follicles and that these concentrations resemble the sAMH value of the patient.

Methods

Patients were stimulated with a gonadotropin-releasing hormone antagonist ovarian hyperstimulation protocol. On the day of oocyte retrieval, serum samples and FF from all individual follicles from one stimulated IVF cycle were collected and individually analyzed for AMH concentrations.

Results

Intracyclic mean fAMH values (n _follicle = 2–14) were significantly correlated to sAHM values (ρ = 0.85, p < 0.001) and showed a trend to be negatively associated with age (ρ = ?0.43, p = 0.06). Mean intrapatient fAMH concentrations differed significantly (p < 0.001). Furthermore, significant correlations of sAMH with individual fAMH values of the first five follicles of each patient were observed.

Conclusions

In conclusion, our results clearly showed that individual fAMH concentrations reflected sAMH values and that fAMH concentrations did not significantly differ within one patient. In future studies, it will be interesting to correlate individual fAMH values to the respective embryo development and overall pregnancy outcome in order to improve IVF treatments and to refrain from embryo overproduction.

     

The effect of 12-month dehydroepiandrosterone supplementation on the menstrual pattern,ovarian reserve markers,and safety profile in women with premature ovarian insufficiency

Purpose

To evaluate the effect of 12-month DHEA supplementation on menstrual pattern and ovarian reserve markers in women with premature ovarian insufficiency (POI)

Methods

This is a prospective observational study. Women with POI were given DHEA supplements (25 mg three times daily) for 12 months. Sonographic assessment for ovarian volume and antral follicle count (AFC) and serum measurement for anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH), estradiol, testosterone, liver function, and hemoglobin level were performed at baseline and monthly for 13 months after the supplementation. Menstrual pattern, ovarian reserve markers, and side-effects were recorded.

Results

Between August 2011 and July 2014, 38 women with POI were recruited and 31 completed the study. The median age of women was 36 years, and the median baseline FSH and AMH concentrations were 82.2 IU/L and 0.01 ng/ml, respectively. No women had resumption of regular menstruation after DHEA supplementation. AMH, FSH, and AFC did not change significantly. No serious side effects were reported.

Conclusions

Our results do not support any significant improvement in ovarian function by 12-month DHEA supplementation in women with POI.

     

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.

     

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.

     

GnRH Antagonist Cetrorelix Administration Before hCG for Protection of Ovarian Hyperstimulation Syndrome

Objective

Studying the effect of GnRH antagonist administration on the day of hCG to cases of IVF/ICSI with estradiol level above 5000 ng/dl for protection of ovarian hyperstimulation syndrome.

Design

Prospective study.

Materials and Methods

Sixty patients undergoing controlled hyperstimulation COH, for IVF/ICSI using long agonist and E2 level on the day of hCG, are above 5000 ng/dl, 52 patients received single dose of cetrorelix 0.25 mg on the day of hCG, and 8 patients received two doses of 0.25 mg/day cetrorelix started one day before the day of hCG.

Results

There was no significant difference regarding patients BMI, number of stimulation days, recombinant FSH dose, and number of retrieved oocytes. Clinical pregnancy rate was 76.6% (46/60), in patients received single dose of antagonist PR were significantly higher 80.7% (42/52) versus 50% (4/8) in patients received two doses p = 0.047. Live birth rate was 50% (30/60), abortion rate was 20% (12/60), and preterm delivery was 20% (12/60). Mean E2 was 6853.2 ng/dl. Six patients developed moderate ovarian hyperstimulation OHSS (6/60) 10% and no cases of severe OHSS.

Conclusions

GnRH antagonist administration on the day of hCG in cases undergoing IVF/ICSI with long agonist protocol is effective in protection of OHSS and does not affect the clinical pregnancy rate nor live birth rate.

     

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.

     

The impact of endometrioma and laparoscopic cystectomy on ovarian reserve and the exploration of related factors assessed by serum anti-Mullerian hormone: a prospective cohort study

Background

To evaluate the impact of the presence of endometrioma and laparoscopic cystectomy on ovarian reserve as assessed by serum anti-Müllerian hormone (AMH) level. In addition, factors related to the decline in ovarian reserve were analyzed.

Methods

From June 2013 to January 2014, we prospectively included 40 women with endometriomas as the study group (group A), 36 women with tubal factor infertilities as control group 1 (group B) and 22 women with the other benign ovarian cysts as control group 2 (group C). The women with ovarian cysts underwent laparoscopic cystectomy. Serum AMH levels were determined preoperatively and at 1 month after surgery.

Results

The endometrioma group had lower AMH levels (1.53?±?1.37 ng/ml) compared with the other benign ovarian cyst group (2.20?±?1.23 ng/ml) and the tubal factor infertility group (2.82?±?1.74 ng/ml). The rate of serum AMH decline 1 month after surgery in the endometrioma group (0.62?±?0.35) was larger than the decline in the other benign ovarian cyst group (0.32?±?0.30). The preoperative AMH level showed a significant correlation with patient age (group A, r?=??0.32; group B, r?=??0.54; group C, r?=??0.71); there was a statistically significant correlation between the rate of serum AMH decline and endometrioma diameter as well as with the preoperative serum AMH level. In addition, the rate of serum AMH decline was larger for bilateral endometriomas than for unilateral endometriomas, but there was no similar correlation in the other benign ovarian cyst group. The rate of AMH decline after surgery in the subgroup of >7 cm was significantly higher than in the subgroup of ≤7 cm.

Conclusions

Ovarian endometriomas per se may damage ovarian reserve, and cystectomy of endometriomas may cause greater damage to ovarian reserve compared with other benign ovarian cysts. The operation-related damage to the ovarian reserve was positively related to whether the endometriomas were bilateral, as well as cyst size (especially for cysts >7 cm), but was negatively related to the preoperative serum AMH level. Age was a negative factor that affected the ovarian reserve.

     

Age,anti-müllerian hormone,antral follicles count to predict amenorrhea or oligomenorrhea after chemotherapy with cyclophosphamide

Background

A cohort study was performed to identify ovarian reserve markers (ORM) that predicts amenorrhea or oligomenorrhea 6 months after cyclophosphamide CTX in women with breast cancer.

Methods

52 eumenorrheic patients with breast cancer were enrolled. FSH, anti-Müllerian hormone (AMH), antral follicles count (AFC) were measured before and 6 months after CTX. A logistic regression for independent samples and determination of the ROC curve were performed.

Results

The age of 32 years presented 96 % of sensitivity and 39 % of specificity to predict amenorrhea or oligomenorrhea with ROC area under the curve (AUC) of 0.77. ovarian reserve marker (ORM) with power to predict amenorrhea or oligomenorrhea in women after CTX were AMH <3.32 ng/mL (sensitivity of 85 %, specificity of 75 % and AUC 0.87), AFC <13 follicles (sensitivity 81 %, specificity 62 %, AUC 0.81). AMH cutoff to predict amenorrhea was 1.87 ng/mL (sensitivity 82 %, specificity 83 %, AUC 0.84) and AFC cutoff was 9 follicles (sensitivity 71 %, specificity 78 %, AUC 0.73).

Conclusions

≥32-years-old women, AMH <3.32 ng/mL and AFC <13 follicles determined significantly higher risk of amenorrhea or oligomenorrhea after CTX with cyclophosphamide. The ORM age (≥32 years) analyzed together with AMH or AFC increases sensitivity and specificity in predicting amenorrhea or oligomenorrhea.

     

Endometrial injury,the quality of embryos,and blastocyst transfer are the most important prognostic factors for in vitro fertilization success after previous repeated unsuccessful attempts

Purpose

The purpose of this study was to find out the most important prognostic factors for achieving a pregnancy after in vitro fertilization (IVF) in women with history of repeated unsuccessful IVF attempts.

Methods

We analyzed factors affecting pregnancy rate in a retrospective study including 429 IVF/ICSI cycles performed in women younger than 40 years with at least three previous consecutive failed IVF/ICSI attempts.

Results

Clinical pregnancy was observed in 140/429 (32.6%) cycles. Clinical pregnancy rate (CPR) was significantly higher in cycles with LEI compared to cycles without LEI before embryo transfer (44.4 vs 26.54%, p = 0.007). The CPR was also higher in cycles with day 5 blastocyst- compared with day 3 cleavage-stage embryo transfers (45.51 vs 26.54%, p < 0.001). In multivariate logistic regression model, only transfer of at least one good quality embryo (OR = 4.32, 95% CI 2.41–7.73), local endometrial injury (OR = 1.73, 95% CI 1.02–2.92), and transfer on day 5 (OR = 3.02, 95% CI 1.53–5.94) remained important independent prognostic factors for clinical pregnancy.

Conclusions

These results suggest that hysteroscopy with local injury to the endometrium prior to ovarian stimulation for IVF/ICSI can improve implantation and pregnancy rates in women experiencing recurrent IVF failure. However, large studies are needed to confirm these findings.

     

Decrease in preovulatory serum estradiol is a valuable marker for predicting premature ovulation in natural/unstimulated in vitro fertilization cycle

Background

Premature ovulation occurs at a high rate in natural-cycle in vitro fertilization (IVF), and cycle cancellation further hampers the overall efficiency of the procedure. While lower levels of estradiol (E2) are observed in preovulatory follicles, it is unclear whether declines in E2 can be used as an effective marker of premature ovulation.

Methods

This retrospective analysis includes 801 natural/unstimulated IVF/ICSI cycles undergoing scheduled ovum pick-up (OPU) and 153 natural/unstimulated IVF/ICSI cycles undergoing emergency OPU at a university IVF center from May 2014 to February 2017.

Results

Among the 801 IVF/ICSI cycles undergoing scheduled OPU, preovulatory E2 levels increased by more than 10% in 403 (50.31%) cycles of the sample (Group A), while 192 (23.97%) cycles experienced a plateau (increased or decreased by 10%; Group B), and 206 (25.72%) cycles decreased by more than 10% (Group C). Group C had more patients who experienced premature LH surges, premature ovulation, as well as the fewest oocytes retrieved, frozen embryos, and top-quality embryos. A multivariate logistic regression analysis indicated that premature ovulation was associated with preovulatory E2/?1E2 ratio and premature LH surge. Moreover, preovulatory E2/?1E2 ratio served as a valuable marker for differentiating premature ovulation, with an AUC (area under the receiver operating curve) of 0.708 and 0.772 in cycles with premature LH surges and cycles without premature LH surges, respectively. Emergency OPU resulted in a significantly decreased rate of premature ovulation and increased number of frozen embryos.

Conclusion

Decreases in preovulatory serum E2 was a valuable marker for premature ovulation in natural/unstimulated IVF cycle. Emergency OPU based on the preovulatory E2/?1E2 ratio decreased the rate of premature ovulation in cycles that experienced E2 decreases.

     

Evaluation of Dehydroepiandrosterone Supplementation on Diminished Ovarian Reserve: A Randomized,Double-Blinded,Placebo-Controlled Study

Introduction

We conducted a randomized, double-blinded, placebo-controlled study, to evaluate the effect of dehydroepiandrosterone (DHEA), on diminished ovarian reserve (DOR).

Materials and Methods

Twenty patients with DOR received DHEA (oral 25 mg three times a day). Post-supplementation 12 weeks, D2/3 age-specific follicle-stimulating hormone (FSH), anti-mullerian hormone (AMH) levels, and antral follicle count (AFC), were repeated to evaluate response. Spontaneous pregnancy rates and regularization of menstrual cycles were also studied as secondary outcome.

Results

Predominant risk factors were age >35 years (28 %) and poor responders to ovarian stimulation (23 %). There was significant improvement of AMH levels (1.15 ± 1.49 vs. 1.53 ± 1.62) found before and after supplementation in the DHEA group. When the AMH values between DHEA and placebo group were compared, pre- and post-supplementation, no significant difference was found. There was decrease in FSH levels and increase in AFC value post-supplementation in both DHEA and placebo groups which was not statically significant. DHEA supplementation benefited clinically, as evidenced by the improvement in the menstrual abnormality spontaneous conception in two cases each.

Conclusions

A significant improvement in AMH levels pre- and post-supplementation of DHEA was noted. The same was not seen for FSH and AFC values.

     

Women’s alcohol consumption and cumulative incidence of live birth following in vitro fertilization

Objective

The objective of this study was to determine the effect of alcohol consumption on outcomes among women undergoing in vitro fertilization (IVF).

Design

This study is a retrospective cohort study.

Setting

This study was performed in a private academically affiliated IVF center.

Patients

Patients included women presenting for their first IVF cycle from July 2004 through October 2012.

Intervention

Women completed self-administered questionnaires before their first IVF cycle, which included report of usual alcohol consumption. Women were categorized as non-drinkers, social drinkers, or daily drinkers, as well as by the number of drinks consumed per week. Competing risks analysis was used to calculate the cumulative incidence of live birth after 6 cycles stratified by alcohol consumption.

Main outcome measures

Main outcome measures included spontaneous abortion, clinical pregnancy, and live birth following IVF.

Results

There were 591 (27.7%) non-drinkers, 1466 (68.7%) social drinkers, and 77 (3.6%) daily drinkers (total n = 2134). In the first cycle, compared to non-drinkers, daily drinkers had a twofold increased risk of spontaneous abortion (adjusted risk ratio [aRR] 2.2; 95% confidence interval [CI] 1.1–4.5) among all cycle starts, and while their risk of live birth was 30% lower (aRR 0.7; 95% CI 0.4–1.3), the sample size was small, and it was not significantly lower. By the end of 6 cycles, social drinkers and daily drinkers did not differ from non-drinkers in their cumulative incidence of live birth (56.1, 50.6, and 52.1%, respectively; both P ≥ 0.28).

Conclusion

There was a trend towards lower risk of live birth among daily drinkers. Daily drinkers had an increased risk of spontaneous abortion in the first cycle, but the number of daily drinkers was small.

     

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.

     

Male chromosomal polymorphisms reduce cumulative live birth rate for IVF couples

Purpose

Chromosomal polymorphisms are associated with infertility, but their effects on assisted reproductive outcomes are still quite conflicting, especially after IVF treatment. This study evaluated the role of chromosomal polymorphisms of different genders in IVF pregnancy outcomes.

Methods

Four hundred and twenty-five infertile couples undergoing IVF treatment were divided into three groups: 214 couples with normal chromosomes (group A, control group), 86 couples with female polymorphisms (group B), and 125 couples with male polymorphisms (group C). The pregnancy outcomes after the first and cumulative transfer cycles were analyzed, and the main outcome measures were live birth rate (LBR) after the first transfer cycle and cumulative LBR after a complete IVF cycle.

Results

Comparison of pregnancy outcomes after the first transfer cycle within group A, group B, and group C demonstrated a similar LBR as well as other rates of implantation, clinical pregnancy, early miscarriage, and ongoing pregnancy (P > 0.05). However, the analysis of cumulative pregnancy outcomes indicated that compared with group A, group C had a significantly lower LBR per cycle (80.4 vs 68.00%), for a rate ratio of 1.182 (95% CI 1.030 to 1.356, P = 0.01) and a significantly higher cumulative early miscarriage rate (EMR) among clinical pregnancies (7.2 vs 14.7%), for a rate ratio of 0.489 (95% CI 0.248 to 0.963, P = 0.035).

Conclusion

Couples with chromosomal polymorphisms in only male partners have poor pregnancy outcomes after IVF treatment manifesting as high cumulative EMR and low LBR after a complete cycle.

     

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.

     

Cumulative pregnancy and live birth rates through assisted reproduction in women 44–45 years of age: is there any hope?

Purpose

The purpose of the study is to calculate the cumulative pregnancy rate and cumulative live birth rate in women undergoing in vitro fertilization (IVF) at ages 44–45.

Methods

The study calculated cumulative live pregnancy rate and cumulative live birth rate of 124 women aged 44 to 45 years old who commenced IVF treatment.

Main outcome measures

The main outcome measures are cumulative live pregnancy rate and cumulative live birth rate.

Results

Cumulative live pregnancy rates following 1, 2, 3, and 4 cycles were 5.6, 11, 17, and 20%, respectively, with no additional pregnancies in further cycles. Cumulative live birth rates following 1, 2, and 3 cycles were 1.6, 3, and 7%, respectively, with no additional live births in further cycles.

Conclusions

The cumulative pregnancy rate rises during the first 4 cycles and cumulative live birth rate rises during the first 3 cycles, with no additional rise in pregnancies or deliveries thereafter, suggesting that it is futile to offer more than 3 cycles of treatment to 44–45-year-old women.

     

GnRh Agonist Treatment Improves Implantation and Pregnancy Rates of Frozen–Thawed Embryos Transfer

Objective

To study the effect of GnRh agonist administration prior to estrogen–progesterone preparation of the endometrium on the implantation rate in frozen–thawed embryo transfer (FET) cycles in infertile patients treated with IVF/ICSI.

Design

Prospective controlled study.

Setting

Private center in Alexandria, Egypt.

Patients

Patients undergoing frozen–thawed embryo transfer FET.

Intervention(s)

Patients were divided into two groups, A and B. Group A patients consisted of 110 patients (110 cycles) who received daily subcutaneous injections of 0.1 mg of the GnRh agonist triptorelin starting from the mid-luteal phase of the cycle preceding the actual FET cycle. The dose was reduced to 0.05 mg from the second day of the cycle when daily oral estradiol valerate 6 mg was also started. Daily vaginal supplementation of micronized progesterone 400 mg b.d. was started after 12 days when the GnRh agonist was also stopped. Frozen–thawed embryos were transferred on day + 1 of their chronological age and when the endometrium reached 12 mm in thickness. Group B consisted of 100 patients (100 cycles) who started daily estradiol valerate 6 mg administration from the second day of the FET cycle and followed the same regimen but without prior treatment with triptorelin.

Main Outcome Measures

Implantation and pregnancy rates were compared among the two groups.

Results

There was a significant increase in implantation rate in the GnRh agonist group (group A) compared to the estrogen and progesterone only group (group B) (44.1 vs. 21.1 %; P = 0.002*). The pregnancy rate was also significantly higher in group A compared to group B (65.5 vs. 42 %, P = 0.013*).

Conclusions

GnRh agonist administration during endometrial preparation for FET increases the implantation and pregnancy rates.