P–698 Antimüllerian Hormone (AMH) value as a predictive marker of cycle ploidy outcome

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Arnanz ◽  
I Elkhatib ◽  
A Bayram ◽  
A El-Damen ◽  
A Abdala ◽  
...  

Abstract Study question Do woman with diminished ovarian reserve exhibit poor blastocyst formation and ploidy outcomes, irrespective of age? Summary answer Patients with extreme diminished ovarian reserve (AMH≤0.65ng/ml) have a lower chance to have at least one euploid blastocyst compared to their age-related reference population (AMH=1.3–6.25ng/ml). What is known already AMH is an established marker of the ovarian reserve for predicting ovarian response to ovarian stimulation and it is strongly correlated with female age. However, it has been suggested that AMH is not only a quantitative, but also a qualitative biomarker of oocyte/embryo competence. Previous studies show conflicting outcomes as to whether reduced ovarian reserve per se is associated with decreased oocyte developmental competence, leading to increased aneuploidy rates in embryos independent of the patient’s age. Study design, size, duration A retrospective analysis was performed between March 2017 and July 2020 at ART Fertility Clinics (Abu Dhabi) including all couples that were triggered for final oocyte maturation and planned for Preimplantation Genetic Testing for Aneuploidies (PGT-A). Patients were stratified into four age categories [≤30, 31–35, 36–40, >40 years]. For each age category patients were further divided into three AMH groups: ≤0.65ng/ml, 0.65–1.3ng/ml and 1.31–6.25ng/ml (reference group). Participants/materials, setting, methods Trophectoderm biopsy samples were subjected to Next Generation Sequencing. AMH serum levels (ng/ml) were determined using the commercial fully automated Elecsys® (Roche) assay. Patients with a Progesterone rise of > 1.5ng/ml on the day of final oocyte maturation and patients with AMH values >6.25ng/ml were excluded from the analysis. Per patient that was triggered, the chance to have at least one euploid blastocyst in that cycle, was calculated. Main results and the role of chance A total of 1.300 couples were included with an mean maternal age of 35.6±6.2 years, AMH of 2.1 ±1.5ng/ml and body mass index of 27.5±5.0 kg/m2. The chance to have at least one blastocyst biopsied per cycle was affected in all patients with extreme low AMH (≤0.65ng/ml), irrespective of age; ≤30 years: 58.33%–100.00%–94.84% (p < 0.001); 31–35 years: 50.00%–74.55%–95.32% (p < 0.001); 36–40 years: 56.52%–81.93%–92.56% (p < 0.001) and ≥40 years: 38.06%–73.02%–88.24% (p < 0.001), for AMH ≤0.65ng/ml, 0.65–1.3ng/ml and 1.31–6.25ng/ml, respectively. In all age categories, patients with AMH values ≤0.65ng/ml had a significantly reduced probability of having a euploid blastocyst compared to the reference group (1.31–6.25ng/ml). For women ≤30 years the chances of getting a euploid blastocyst decreased from 88.89% (n = 252) to 41.67% (n = 12) (OR 0.01 [0.03–0.30], p < 0.001), for 31–35 years from 88.09% (n = 235) to 43.75% (n = 32) (OR 0.10 [0.05–0.23], p < 0.001), for 36–40 years from 77.67% (n = 215) to 21.74% (n = 69) (OR 0.08 [0.04–0.15], p < 0.001) and among women >40 years from 29.42% (n = 102) to 6.45% (n = 155) (OR 0.16 [0.08–0–36], p < 0.001). Woman within AMH range of 0.65–1.3ng/ml presented the same decreased probability of having a euploid blastocyst only when 31–35 (52.73%, n = 55) or 36–40 years old (56.63%, n = 83) (OR 0.15 [0.08–0.29], p < 0.001 and OR 0.37 [0.22–0.64], p < 0.001, respectively). Limitations, reasons for caution The main limitation of this study is its retrospective design. Wider implications of the findings: AMH is a clear biomarker of oocyte-embryo competence. Incorporation of AMH-specific counseling recommendations into clinical practice guidelines, could lead to a more informed guidance on cycle ploidy outcomes, rather than age alone. Trial registration number Not applicable

2013 ◽  
Vol 4 (2) ◽  
pp. 45-55 ◽  
Author(s):  
Mala Arora ◽  
Mandeep Kaur

ABSTRACT Diminished ovarian reserve predicts diminished ovarian response to stimulation but does not predict cycle fecundity. It has been recently defined by ESHRE, the Bologna's criteria, according to which at least two of the following three features should be present: (1) Age >40 years/any other risk factor for DOR, (2) abnormal ovarian reserve test, i.e. antral follicle count, AMH, (3) poor ovarian response in a previous stimulated cycle, i.e. less than three follicles after standard gonadotropin stimulation. Poor response to maximal stimulation on two previous occasions also defines DOR. The treatment options are limited. Avoiding the GnRH agonist long protocol and stimulation with microdose flare or antagonist protocol yields better results. Adjuvant therapy with LH, DHEAS and growth hormone shows some benefit in improving the oocyte yield. It is advisable to perform ICSI for all obtained oocytes and some advocate assisted hatching. Pregnancy rates are, however, poor and often these patients require ovum donation. Developing tests that will diagnose DOR in a low-risk population will allow women to plan their reproductive careers early. How to cite this article Kaur M, Arora M. Diminished Ovarian Reserve, Causes, Assessment and Management. Int J Infertility Fetal Med 2013;4(2):45-55.


2020 ◽  
Vol 35 (3) ◽  
pp. 727-733 ◽  
Author(s):  
Semra Kahraman ◽  
Murat Cetinkaya ◽  
Beril Yuksel ◽  
Mesut Yesil ◽  
Caroline Pirkevi Cetinkaya

Abstract Mosaic embryos have the potential to implant and develop into healthy babies. The transfer of mosaic embryos is now considered to be a possible option for women undergoing ART with preimplantation genetic testing for aneuploidies and in the absence of euploid embryos, particularly those with diminished ovarian reserve and/or advanced maternal age. It can aid in avoiding the discard of potentially viable embryos, which might otherwise result in healthy babies. In over 500 studies on mosaicism, there have been no reports of mosaicism in babies born following the transfer of mosaic embryos. Here, we present a case report of a 39-year-old woman with diminished ovarian reserve with only one blastocyst available for trophectoderm biopsy. The transfer of the embryo, which showed 35% mosaicism of monosomy 2, resulted in pregnancy. Amniocentesis revealed a mosaic trisomic mos46,XX(98)/47,XX,+2(2) karyotype. There were no pathological findings in detailed ultrasonography, and the fetus showed a normal fetal growth with no evidence of intrauterine growth retardation. A healthy female baby was born at Week 37. The peripheral blood chromosome analysis validated with fluorescence in situ hybridization showed 2% mosaic monosomy 2 [mos45,XX,-2(2)/46,XX(98)]. This is the first reported case of true fetal mosaicism resulting in a live birth following the transfer of a known mosaic embryo. Worldwide, prenatal diagnosis has shown the depletion of mosaicism in embryos transferred after they have been reported as mosaics. Our case demonstrates the need for close prenatal monitoring and diagnosis by early amniocentesis, preferably at >14 weeks gestation.


Author(s):  
Reshef Tal ◽  
David B Seifer ◽  
Renana Tal ◽  
Emily Granger ◽  
Ethan Wantman ◽  
...  

Abstract Context Antimullerian hormone (AMH) level is strongly associated with ovarian response in reproductive technology (ART) cycles but is a poor predictor of live birth. It is unknown whether AMH is associated with cumulative live birth rates (CLBR) in women with diminished ovarian reserve (DOR). Objective To examine the association between serum AMH and CLBR among women with DOR undergoing ART. Design Retrospective analysis of Society for Assisted Reproductive Technology Clinic Outcome Reporting System database 2014-16. Setting Not applicable Patients A total of 34,540 index retrieval cycles of women with AMH<1 ng/ml Interventions None Main Outcome Measures Cumulative live birth Results A total of 34,540 (25.9%) cycles with AMH<1 ng/ml out of 133,442 autologous index retrieval cycles were analyzed. Cycles with preimplantation genetic testing or egg/embryo banking were excluded. Data was stratified according to AMH and age and regression analysis of AMH and CLBR was performed for each age strata. Multiple logistic regression demonstrated that AMH is an independent predictor of CLBR (Odds ratio 1.39, 95%CI 1.18-1.64). Serum AMH was strongly associated with number of oocytes retrieved, embryos cryopreserved, mean number of cumulative embryos transferred, and percentage of cycles that had an embryo transfer,. Linear regression analysis demonstrated that AMH highly correlated with CLBR in each age strata. Conclusions Serum AMH is highly correlated with CLBR in women with DOR independent of age. The addition of AMH to current age-based prognostication counseling particularly in women with DOR would provide more informative and personalized CLBR prediction prior to ART.


2021 ◽  
Author(s):  
Nikolaos P Polyzos ◽  
A R Neves ◽  
P Drakopoulos ◽  
C Spits ◽  
B Alvaro Mercadal ◽  
...  

Abstract STUDY QUESTION Does the presence of single nucleotide polymorphisms (SNPs) in the FSH receptor gene (FSHR) and/or FSH beta subunit-encoding gene (FSHB) influence ovarian response in predicted normal responders treated with rFSH? SUMMARY ANSWER The presence of FSHR SNPs (rs6165, rs6166, rs1394205) has a statistically significant impact in ovarian response, although this effect is of minimal clinical relevance in predicted normal responders treated with a fixed dose of 150 IU rFSH. WHAT IS KNOWN ALREADY Ovarian reserve markers have been a breakthrough in response prediction following ovarian stimulation. However, a significant percentage of patients show a disproportionate lower ovarian response, as compared with their actual ovarian reserve. Studies on pharmacogenetics have demonstrated a relationship between FSHR or FSHB genotyping and drug response, suggesting a potential effect of individual genetic variability on ovarian stimulation. However, evidence from these studies is inconsistent, due to the inclusion of patients with variable ovarian reserve, use of different starting gonadotropin doses, and allowance for dose adjustments during treatment. This highlights the necessity of a well-controlled prospective study in a homogenous population treated with the same fixed protocol. STUDY DESIGN, SIZE, DURATION We conducted a multicenter multinational prospective study, including 368 patients from Vietnam, Belgium, and Spain (168 from Europe and 200 from Asia), from November 2016 until June 2019. All patients underwent ovarian stimulation followed by oocyte retrieval in an antagonist protocol with a fixed daily dose of 150 IU rFSH until triggering. Blood sampling and DNA extraction was performed prior to oocyte retrieval, followed by genotyping of four SNPs from FSHR (rs6165, rs6166, rs1394205) and FSHB (rs10835638). PARTICIPANTS/MATERIALS, SETTING, METHODS Eligible were predicted normal responder women <38 years old undergoing their first or second ovarian stimulation cycle. Laboratory staff and clinicians were blinded to the clinical results and genotyping, respectively. The prevalence of hypo-responders, the number of oocytes retrieved, the follicular output rate (FORT), and the follicle to oocyte index (FOI) were compared between different FSHR and FSHB SNPs genotypes. MAIN RESULTS AND THE ROLE OF CHANCE The prevalence of derived allele homozygous SNPs in the FSHR was rs6166 (genotype G/G) 15.8%, rs6165 (genotype G/G) 34.8%, and rs1394205 (genotype A/A) 14.1%, with significant differences between Caucasian and Asian women (P < 0.001). FSHB variant rs10835638 (c.-211 G>T) was very rare (0.5%). Genetic model analysis revealed that the presence of the G allele in FSHR variant rs6166 resulted in less oocytes retrieved when compared to the AA genotype (13.54 ± 0.46 vs 14.81 ± 0.61, estimated mean difference (EMD) −1.47 (95% CI −2.82 to −0.11)). In FSHR variant rs1394205, a significantly lower number of oocytes was retrieved in patients with an A allele when compared to G/G (13.33 ± 0.41 vs 15.06 ± 0.68, EMD −1.69 (95% CI −3.06 to −0.31)). A significantly higher prevalence of hypo-responders was found in patients with the genotype A/G for FSHR variant rs6166 (55.9%, n = 57) when compared to A/A (28.4%, n = 29), ORadj 1.87 (95% CI 1.08–3.24). No significant differences were found regarding the FORT across the genotypes for FSHR variants rs6166, rs6165, or rs1394205. Regarding the FOI, the presence of the G allele for FSHR variant rs6166 resulted in a lower FOI when compared to the A/A genotype, EMD −13.47 (95% CI −22.69 to −4.24). Regarding FSHR variant rs6165, a lower FOI was reported for genotype A/G (79.75 ± 3.35) when compared to genotype A/A (92.08 ± 6.23), EMD −13.81 (95% CI −25.41 to −2.21). LIMITATIONS, REASONS FOR CAUTION The study was performed in relatively young women with normal ovarian reserve to eliminate biases related to age-related fertility decline; thus, caution is needed when extrapolating results to older populations. In addition, no analysis was performed for FSHB variant rs10835638 due to the very low prevalence of the genotype T/T (n = 2). WIDER IMPLICATIONS OF THE FINDINGS Based on our results, genotyping FSHR SNPs rs6165, rs6166, rs1394205, and FSHB SNP rs10835638 prior to initiating an ovarian stimulation with rFSH in predicted normal responders should not be recommended, taking into account the minimal clinical impact of such information in this population. Future research may focus on other populations and other genes related to folliculogenesis or steroidogenesis. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by an unrestricted grant by Merck Sharp & Dohme (MSD). N.P.P. reports grants and/or personal fees from MSD, Merck Serono, Roche Diagnostics, Ferring International, Besins Healthcare, Gedeon Richter, Theramex, and Institut Biochimique SA (IBSA). N.L.V. and M.T.H. report consultancy and conference fees from Merck, Ferring, and MSD, outside the submitted work. P.D. has received honoraria for lecturing and/or research grants from MSD, Ferring International, and Merck. D.S. reports grants and/or personal fees from MSD, Ferring International, Merck Serono, Cook, and Gedeon Richter. A.R.N., B.A.M., C.S., J.M., L.H.L., P.Q.M.M., H.T., and S.G. report no conflict of interests. TRIAL REGISTRATION NUMBER NCT03007043


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Ab. ali ◽  
B Lawrenz ◽  
A L Tegedor ◽  
F R Ruiz ◽  
A El-Damen ◽  
...  

Abstract Study question Does the ratio of serum progesterone (P4) to the number of follicles (P4/Follicle) on the day of final oocyte maturation affect the ploidy status of the embryos? Summary answer A high P4/Follicle ratio negatively affects the euploid rate of the embryos. What is known already During ovarian stimulation, exogenous gonadotropins are administered to achieve multifollicular growth. Intense gonadotropin stimulation towards the end of the follicular phase seems to cause a premature progesterone rise in stimulated IVF cycles. The impact of serum progesterone elevation during the follicular phase has been studied intensively. Though most studies have focused on the effect of progesterone elevation on the endometrial receptivity, little is known about its possible impact on embryo development and ploidy status. The only study that investigated the effect of progesterone on the embryo ploidy status, was unable to show any significant impact. Study design, size, duration This retrospective study was performed at ART Fertility Clinics Abu Dhabi, UAE and Muscat, Oman. All stimulation cycles (n = 975) were performed between January 2015 to December 2019 with patients aged between 18–45, Body mass index (BMI) of 18–35, stimulated either with rFSH or hMG. All embryos underwent ICSI and Preimplantation Genetic Testing for Aneuploidies (PGT-A),Patients with surgical sperm extraction, warmed oocytes or natural cycle IVF were excluded. Participants/materials, setting, methods Serum P4 was measured on the last ultrasound prior triggering for final oocyte maturation. The P4/Follicle ratio was calculated as the ratio of P4 on trigger day to the number of follicles > 10 mm on the last ultrasound. Serum P4 and P4/Follicle ratio were then analyzed using linear and univariate regression model to find potential correlation with the number of oocytes retrieved, number of mature oocytes, embryo quality (day 3 and 5), and euploid rate. Main results and the role of chance A total of 975 cycles were analyzed, with a mean age of 33.88±0.05 years, a mean BMI of 26.7±0.035 kg/m2. The mean number of oocytes collected was 12.53±0.058. Mean serum P4 on trigger day was 0.83±0.005 ng/ml and higher serum P4 values were observed as the number of oocytes retrieved and the number of mature oocytes increased (β = 0.026, p < 0.0001 and β = 0.028, p < 0.001, respectively). On the other hand, the mean P4/Follicle ratio was 0.056±0.00041 ng/ml and, unlike serum P4, the P4/Follicle ratio showed a negative correlation with the number of oocytes retrieved as well as with the number of mature oocytes (β=–0.001, p < 0.001 and β=–0.001, p < 0.001, respectively). While day 3 embryos were not affected by serum P4 or P4/Follicle ratio, the blastocyst quality was negatively affected by both increasing serum P4 levels and the P4/Follicle ratio (β=–0.012 p < 0.05, β=–0.002, p < 0.001, respectively). Euploid rates were positively correlated in cycles with increased serum P4 β = 0.18, p < 0.001), while negatively correlated in cycles with a high P4/Follicle ratio (β=–0.015, p < 0.001). After adjusting for potential confounders, only P4/Follicle remained as a significant negative factor for euploid rate (β=–0.004, p < 0.001, 95% CI: –0.007- –0.001, p < 0.001), which was not observed for serum P4 (p = 0.46). Limitations, reasons for caution This is an observational study based on retrospective data; an improved extrapolation of the results might be obtained by performing a prospective study. Wider implications of the findings: The findings of this study should encourage clinicians to optimize the ovarian stimulation protocols not only based on serum P4, but also considering the P4/Follicle ratio. Trial registration number Not applicable


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