Stimulated IVF Cycles Research Articles

Significant Serum Progesterone Variations on the Day of Final Oocyte Maturation in Stimulated IVF Cycles.

Objective: To evaluate intraday serum progesterone levels on the day of final oocyte maturation in women undergoing ovarian stimulation in a GnRH-antagonist protocol.Study design, size, and duration: The study was done as a prospective observational study at a Private IVF centre in Muscat, Oman. 30 patients were recruited from May 2018 to March 2019.Patients: Thirty patients with primary/secondary infertility and an indication for ovarian stimulation for IVF/ICSI treatment. The study was registered at the clinicaltrials.gov under the number: NCT03519776.Main outcome measures: Progesterone levels at 4 time points (8 a.m., 11 a.m., 2 p.m. and 5 p.m.) on the day of final oocyte maturation.Results: A total of 120 samples from 30 patients were included in this prospective study. Progesterone levels on the day of final oocyte maturation showed a significant decline over the day with the mean values at 8 a.m.:1.0 ng/ml, at 11 a.m.:0.8 ng/ml, at 2 a.m.: 0.7 ng/ml and at 5 p.m.:0.6 ng/ml. The difference between the first and the last progesterone level was 0.4 ng/ml, reflecting a 37.8% decline of the progesterone level within 9 h and there was a highly significant decrease in the progesterone levels recorded between 8 a.m. and 11 a.m., between 8 a.m. and 2 p.m., between 8 a.m. and 5 p.m. and 11 a.m. and 5 p.m. (p < 0.001).Conclusion: The study findings have two clinically important conclusions: Firstly, progesterone levels on the day of final oocyte maturation decline significantly from the morning to the afternoon in patients, questioning the reliability of one arbitrarily taken progesterone level regarding the decision to perform a fresh embryo transfer or to cryopreserve the embryos. Secondly, declining progesterone levels 12 h after the last administration of gonadotropins support the theory that enhanced ovarian stimulation at the end of the follicular phase leads to an overload of the capacity of the enzymes metabolizing progesterone further on, therefore resulting in elevated progesterone levels in circulation.

Added benefit of immature oocyte maturation for fertility preservation in women with malignancy

To assess the added value of maturing immature oocytes collected during fertility preservation treatments in women with malignancy. A retrospective case-control study analyzing the results of 327 cancer patients undergoing fertility preservation treatments. Oocyte maturation rates and cycle parameters were compared between 3 types of fertility preservation treatments: (1) stimulated IVF cycle (n = 143), (2) non-stimulated IVM cycle (n = 158), (3) follicle aspiration and oocyte collection from ovarian tissue prepared for ovarian tissue cryopreservation followed by in vitro maturation of the immature oocytes (n = 48). The primary outcome measure was the maturation rate and the number of mature oocytes. The secondary outcomes were oocyte fertilization and embryo development rates. The mean maturation rate in IVF cycles was 38% and in the non-stimulated IVM cycles was 55%. In women who chose to cryopreserve their embryos, similar fertilization and embryo cleavage rates were found in oocytes that matured after stimulated IVF cycles compared to non-stimulated IVM cycles. Gonadotropin-releasing hormone agonist triggering, treatment with aromatase inhibitor, or oral contraceptives use before the cycle did not affect the maturation rate. Ovarian stimulation yields the highest number of oocytes or embryos for cryopreservation. Although the maturation rate of immature oocytes collected in stimulated IVF cycles is low, it is still a viable source of oocytes that can be used to improve the efficacy of fertility preservation treatments by increasing the number of mature oocytes available for freezing or fertilization.

Both high and low HCG day progesterone concentrations negatively affect live birth rates in IVF/ICSI cycles.

Can previous reports of a decreased probability of success in stimulated IVF cycles with premature rise of progesterone, as determined by progesterone concentration on HCG day (PHCG), be confirmed? Retrospective, observational, single-centre cohort study conducted on 5447 IVF and intracytoplasmic (ICSI) cycles carried out among 2192 patients between 2009 and 2015, with conventional ovarian stimulation. This large database was used to develop a non-linear mixed prognosis model of live birth rate (LBR) incorporating PHCG as a predictor. In addition to known predictors (age, body mass index, anti-Müllerian hormone, type of infertility), PHCG was associated with a linear effect (OR 0.78 per Log[PHCG]ng/ml, 95% CI 0.611 to 0.997, P = 0.047) combined with a strong quadratic effect (OR 0.585 per Log2(PHCG)ng/ml, 95% CI 0.444 to 0.775, P < 0.001) resulting into a parabolic reverse-U curve. A significant interaction (P = 0.038) was found between PHCG and number of oocytes if three or less, but the effect of PHCG remains modest. For higher oocyte numbers, LBR rapidly increases with number of retrieved oocytes; however, LBR becomes more sensitive to PHCG as the number of oocytes increases. Higher live birth prognoses occur for optimal PHCG but are sharply reduced for lower or higher PHCG. Evidence is provided of an important negative effect of PHCG at lower and higher values, independent of oocyte number, thus defining appropriate ranges for fresh embryo transfer or freeze-all strategy. In poor responders, premature progesterone rise may be ignored, thus avoiding unnecessary cancellations or embryo freezing. Conversely, in higher responders, the negative effect of progesterone elevation is more pronounced, suggesting that freeze-all policy should be applied more widely.

Comparison of follicular fluid concentrations of anti-mullerian hormone, bone morphogenetic protein 15 and transforming growth factor ß1 between modified natural and stimulated in-vitro fertilization cycles.

Analysis of biochemical characteristics of follicular fluid (FF) can serve as a non-invasive method for the prediction of oocyte and embryo quality. The aim of the present study was to compare concentrations of anti-mullerian hormone, bone morphogenetic protein 15 and transforming growth factor ß1 in FF of follicles giving rise to high quality embryos between natural and stimulated IVF cycles. Concentration of BMP-15 was significantly higher and concentration of TGF-ß1 was significantly lower in stimulated IVF cycles. Concentrations of markers of oocyte and embryo quality were significantly different between natural and stimulated IVF cycles. This could be the cause for lower pregnancy rates in natural IVF cycles.

Use of Clomiphene Citrate in minimal stimulation in vitro fertilization negatively impacts endometrial thickness: an argument for a freeze-all approach.

ObjectiveMinimal stimulation IVF is a treatment option that uses clomiphene citrate (CC). We sought to evaluate how CC impacts endometrial thickness during minimal stimulation IVF cycles.MethodsWe retrospectively analyzed a cohort of 230 cycles in 119 poor ovarian response patients. The IVF cycles were studied in three groups: 130 minimal stimulation cycles, 29 mild stimulation cycles, and 30 conventional high dose gonadotropin releasing hormone (GnRH) antagonist cycles. Thirty-three minimal stimulation IVF patients had 41 frozen embryo transfers (FET) which allowed us to study whether the CC effects were prolonged.ResultsEndometrial thickness in the minimal stimulation group was significantly lower than the mild and conventional stimulation groups (7.3±2.2mm versus 11.4±3.3mm versus 12.9±3.8mm, respectively, p<0.0001). In patients who underwent minimal stimulation IVF followed by FET, significantly thicker endometrial thickness was achieved during their FET cycles as compared to their minimal stimulation cycles (7.95±2.1mm versus 10.3±1.8mm, p<0.0001).ConclusionWe concluded that endometrial thickness is impacted during minimal stimulation IVF cycles. Since negative effects on endometrial thickness are not observed in the patients’ subsequent FET cycle, a freeze-all approach is justified to mitigate adverse endometrial effects of CC in minimal stimulation IVF cycles.

Intramuscular progesterone (Gestone) versus vaginal progesterone suppository (Cyclogest) for luteal phase support in cycles of in vitro fertilization\u2013embryo transfer: patient preference and drug efficacy

BackgroundThe requirement for luteal phase support (LPS) in stimulated IVF cycles is well established, however drug choice, and route of administration and duration of use are not. This report evaluates patients’ preference and satisfaction by using either vaginal or intramuscular (IM) progesterone (P) supplementation for luteal phase support after in vitro fertilization and embryo transfer (IVF-ET).MethodsIt is a prospective cohort study done in a reproductive and infertility unit in a tertiary care hospital from March 2013 through February 2015 for four hundred and nine patients undergoing IVF-ET. Patients were allowed to choose either vaginal or IM P for LPS. Patient preference and satisfaction, as well as differences in clinical pregnancy rates between the two groups were assessed at one or two time points throughout the study.ResultsThere were no statistically significant differences in the patients’ characteristics and clinical outcomes between the two groups. There were 88 pregnancies (38.8%) among patients treated with vaginal p and 62 pregnancies (34%) among IM P patients. Average satisfaction score at the pregnancy test and ultrasound (U/S) visits was similar between both groups.ConclusionsPatients’ satisfaction and pregnancy rates were similar between vaginal and IM P supplementation.

Outcomes from a university-based low-cost in vitro fertilization program providing access to care for a low-resource socioculturally diverse urban community

To report on outcomes from a university-based low-cost and low-complexity IVF program using mild stimulation approaches and simplified protocols to provide basic access to ART to a socioculturally diverse low-income urban population. Retrospective cohort study. Academic infertility center. Sixty-five infertile couples were enrolled from a county hospital serving a low-resource largely immigrant population. Patients were nonrandomly allocated to one of four mild stimulation protocols: clomiphene/letrozole alone, two clomiphene/letrozole-based protocols involving sequential or flare addition of low-dose gonadotropins, and low-dose gonadotropins alone. Clinical fellows managed all aspects of cycle preparation, monitoring, oocyte retrieval, and embryo transfer under an attending preceptor. Retrieval was undertaken without administration of deep anesthesia, and laboratory interventions were minimized. All embryo transfers were performed at the cleavage stage. Sociomedical demographics, treatment response, and pregnancy outcomes were recorded. From August 2010 to June 2016, 65 patients initiated 161 stimulation IVF cycles, which resulted in 107 retrievals, 91 fresh embryo transfers, and 40 frozen embryo transfer cycles. The mean age of patients was 33.3years, and mean reported duration of infertility was 5.3years; 33.5% (54/161) of cycles were cancelled before oocyte retrieval, with 13% due to premature ovulation. Overall, cumulative live birth rates per retrieval including subsequent use of frozen embryos was 29.0%; 44.6% (29/65) of patients enrolled in the program achieved pregnancy. Use of mild stimulation protocols, simplified monitoring, and minimized laboratory handling procedures enabled access to care in a low-resource socioculturally diverse infertile population.

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

PurposeAnti-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.MethodsPatients 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.ResultsIntracyclic mean fAMH values (nfollicle = 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.ConclusionsIn 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.

FSH Stimulation promotes progesterone synthesis and output from human granulosa cells without luteinization.

Can granulosa cells produce progesterone (P) in response to FSH stimulation? FSH actively promotes P synthesis and output from granulosa cells without luteinization by up-regulating the expression and increasing enzymatic activity of 3β-hydroxysteriod dehydrogenoase (3β-HSD), which converts pregnenolone to P. Serum P level may rise prematurely prior to ovulation trigger in stimulated IVF cycles and adversely affect implantation and clinical pregnancy rates by impairing endometrial receptivity. A translational research study. Human ovarian cortical samples (n=15) and non-luteinizing FSH-responsive human mitotic granulosa cell line (HGrC1) were stimulated with rec-FSH at 12.5, 25 and 50 mIU/ml concentrations for 24 and 48 h. FSH receptor expression was knocked-down and up-regulated in the granulosa cells using short hairpin RNA (shRNA) technology and activin-A administration, respectively. The expressions of the steroidogenic enzymes were analyzed at mRNA level by real-time quantitative RT-PCR, and protein level by western blot and immunoprecipitation assay. The enzymatic activity of 3β-HSD was measured using a spectrophotometric method. In vitro estradiol (E2) and P productions of the cells before and after FSH stimulation were measured by electro-chemiluminescence immunoassay method. Stimulation of the HGrC1 cells with FSH resulted in a dose-dependent increase in the mRNA and protein level of 3β-HSD. Overall, when all time points and FSH doses were analyzed collectively, FSH significantly up-regulated the mRNA expression of its own receptor (3.73±0.06-fold, P<0.001), steroidogenic acute regulatory protein (stAR, 1.7±0.03-fold, P<0.01), side-chain cleavage enzyme (SCC, 1.75±0.03-fold, P<0.01), aromatase (4.49±0.08-fold, P<0.001), 3β-HSD (1.68±0.02-fold, P<0.01) and 17β-hydroxy steroid dehydrogenase (17β-HSD, 2.16±0.02-fold, P<0.01) in the granulosa cells. Expression of 17α-hydroxylase (17α-OH, 1.03±0.01-fold P>0.05) did not significantly change. Similar changes were observed in the protein expression analysis of these enzymes on western blotting after FSH stimulation. FSH significantly increased 3β-HSD, 17β-HSD and aromatase in a dose-dependent manner but did not affect 17α-OH. Protein expression of P was increased along with 3β-HSD after FSH stimulation, which was further evidenced by immunoprecipitation assay. Enzymatic activity of 3β-HSD was significantly enhanced by FSH administration in the HGrC1 cells in a dose-dependent manner. In line with these findings P output (1.05±0.3 vs. 0.2±0.1 ng/ml, respectively, P<0.001) from the samples stimulated with FSH were significantly increased along with E2 (1918±203 vs. 932±102 pg/ml, respectively, P<0.001) compared to unstimulated controls. FSH-induced increase in 3β-HSD expression was amplified and reversed in the HGrC1 cells when FSH receptor expression was up-regulated by activin-A and down-regulated with shRNA, respectively. As only the effect of FSH was studied we cannot extrapolate our findings to the potential effects of HMG and recombinant LH. This data provides a molecular explanation for the largely unexplained phenomenon of P rise during the follicular phase of gonadotropin stimulated IVF cycles. Our findings may progress the research to uncover potential mechanisms for preventing premature P rise that appears to be associated with inferior outcomes in women undergoing IVF. Funded by the School of Medicine and the Graduate School of Health Sciences of Koc University. All authors declare no conflict of interest. None.

Clinical effectiveness of therapeutic regimens of progesterone in IVF programs in women with tuboperitoneal factor of infertility

The article was discussed the efficacy of treatment dose of progesterone Luteina in the dose 400 gr a day intravaginal in patients with tuboperitoneal factor of infertility. In patients with tuboperitoneal infertility in IVF who received a progesterone in the day of the trigger of the ovulation was diagnosed the increase in pregnancy rate compared to patients who received a progesterone in the day of the puncture of follicles. In particular there has been an increase in the frequency of child bearing in the patients who received progesterone in the day of the puncture of follicles.The purpose of study was evaluating the effectiveness of therapeutic regimens of progesterone prescription in IVF programs by examining pregnancy, analysis of its course and outcomes in women with tubal-peritoneal factor of infertility.A comparative analysis of pregnancy rate and the flow through the clinical, biochemical and instrumental methods of research in cycles of stimulation in women of reproductive age with tuboperitoneal infertility depending of the start of progesterone injections.It is proved that in patients with injection of progesterone on the day of trigger of ovulation were no statistically significant differences in rates of pregnancy and implantation compared with patients whom progesterone was injected on the day of follicular puncture. However, there was a statistically significant difference in the number of clinical pregnancy, and multiple pregnancy in a subgroup of women which started using progesterone on the day of trigger of ovulation.In the study of problem of treatment of tuboperitoneal infertility by exploring therapeutic regimens of progesterone prescription in stimulated IVF cycles were found that using of progesterone on the day of trigger of ovulation contributes to a full invasion of trophoblast and qualitative implantation that defines a successful outcome of pregnancy.

Live birth and perinatal outcomes following stimulated and unstimulated IVF: analysis of over two decades of a nationwide data.

Does ovarian stimulation affect perinatal outcomes of preterm birth (PTB) and low birth weight (LBW) following IVF treatment. Despite no significant differences in the risks of PTB and LBW between stimulated and unstimulated IVF in the present study, the study cannot exclude the effect of ovarian stimulation on the perinatal outcomes following IVF. Pregnancies resulting from assisted reproductive treatments (ART) are associated with a higher risk of pregnancy complications compared to spontaneously conceived pregnancies attributed to the underlying infertility and the in vitro fertilization techniques. It is of interest to determine the effect size of ovarian stimulation use in achieving a live birth and whether ovarian stimulation that is routinely used in IVF, affects perinatal outcomes of birth weight and gestational age at delivery compared to unstimulated IVF. Anonymous data were obtained from the Human Fertilisation and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1991 to 2011 comprising a total of 591 003 fresh IVF ± ICSI cycles involving 584 835 stimulated IVF cycles and 6168 unstimulated IVF cycles were analyzed. Data on all women undergoing either stimulated or unstimulated fresh IVF ± ICSI cycles during the period from 1991 to 2011 were analyzed to compare live birth rates, singleton live birth rates, perinatal outcomes of PTB, early PTB (<32 weeks), LBW and very LBW (<1500 grams) among singleton live births. Adjusted logistic regression was performed for each perinatal outcome for confounding factors: female age, period of treatment, cause of infertility, number of previous IVF cycles and previous live birth. Analysis of the large nationwide data demonstrated 3.5 times (95% confidence interval (CI): 3.1-3.9) as many unstimulated IVF cycles being required to achieve one live birth compared to stimulated IVF and 2.9 times (95% CI: 2.6-3.2) as many unstimulated IVF cycles being required to achieve one singleton live birth compared to stimulated IVF. There was no significant difference in the unadjusted odds for PTB (odds ratio (OR) 1.27, 95% CI: 0.80-2.00) and LBW (OR 1.48, 95% CI: 0.90-2.42) between stimulated and unstimulated IVF cycles. There was no significant difference in the risk of the adverse perinatal outcomes after adjusting for potential confounders; PTB (adjusted odds ratio (aOR) 1.43, 95% CI: 0.91-2.26) and LBW (aOR 1.58, 95% CI: 0.96-2.58). Although the analysis was adjusted for a number of important confounders, the dataset had no information on smoking, body mass index (BMI) and the medical history of women during pregnancy to allow adjustment. Anonymized nature of the dataset did not make it permissible to analyse one cycle per woman. Given the smaller number of perinatal events with unstimulated IVF, a larger study is needed to investigate further. Analysis of this large dataset demonstrates that ovarian stimulation has a vital role in maximizing efficacy of IVF. Although there were no significant differences for PTB and LBW following stimulated compared to unstimulated IVF, the CIs were wide enough to include possible clinically important effects. No funding was obtained. There are no competing interests to declare.

Significance of premature progesterone rise in IVF.

The current review will focus on the cause of premature progesterone and its impact on endometrial receptivity and endometrial gene expression. Premature progesterone rise in stimulated IVF cycles seems to have a negative impact on the pregnancy rate. The current knowledge on the cause of a premature progesterone rise is still limited; however, it seems that overstimulating the ovaries during the end of the follicular phase will lead to a premature progesterone rise. The negative impact on the outcome is mainly due to reduced endometrial receptivity as can be seen in the altered endometrial gene expression. Future studies should focus on how ovarian stimulation can be tailored according to individual requirements of the patients, aiming on preventing a possible progesterone rise during follicular phase of stimulated IVF cycles.

Low Ovarian Stimulation Using Tamoxifen/FSH Compared to Conventional IVF: A Cohort Comparative Study in Conventional IVF Treatments

Background: Over the last decade, the laboratory procedures in artificial reproduction have improved, thus fewer eggs are necessary. Therefore mild stimulations have been introduced to reduce the risk for the patient and patient drop-outs in treatment. The present study was designed to evaluate the efficacy of low stimulation with Tamoxifen and FSH in a routine IVF clinic. Material and methods: A total of 2,709 regular short antagonist IVF cycles were compared to 170 Tamoxifen low stimulation IVF cycles. All patients were recruited in the same time period and allocated to the different treatments on their own request. Results: No differences in age and number of previous cycles were found in between the groups. The clinical pregnancy rate was found to be significantly lower in the Tamoxifen treated group (20% vs. 26%), however we did not find any significant pregnancy rate following transfer (31% Tamoxifen group vs. 28% in conventional IVF). We found lower numbers of visits, lower costs for medication, less side effects and better acceptance for treatment in the Tamoxifen group. Conclusion: Although we found a lower pregnancy rate per started cycle, the pregnancy rate per transfer was equal and better accepted by the patients.

Association between response to ovarian stimulation and miscarriage following IVF: an analysis of 124 351 IVF pregnancies

Is there a relationship between ovarian reserve, quantified as ovarian response to stimulation, and miscarriage rate following IVF treatment? There is a strong association between the number of oocytes retrieved and miscarriage rate following IVF treatment, with the miscarriage rate decreasing with an increasing number of oocytes and then levelling off: poor responders have a higher miscarriage rate across all age groups. Poor ovarian response is a manifestation of a decline in the quantity of the primordial follicle pool. Whether poor ovarian response is associated with a decline in oocyte quality contributing to miscarriage is however debated. Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of assisted reproduction treatment (ART) in the UK. The HFEA has collected data on all ART performed in the UK since 1991. Data from 1991 to June 2008 involving 402 185 stimulated fresh IVF cycles and 124 351 pregnancy outcomes were analysed. Data on all women undergoing a stimulated fresh IVF treatment cycle with at least one oocyte retrieved during the period from 1991 to June 2008 were analysed for their early pregnancy outcomes. There was a strong association between the number of oocytes retrieved and the clinical miscarriage rate. The miscarriage rate fell from 20 to 13% with an increasing number of oocytes before levelling off. Stepwise logistic regression identified three cut-off points (4, 10 and 15 oocytes) at or beyond which the probability of clinical miscarriage fell. There was no increase in miscarriage rate with very high oocyte numbers (>20 oocytes). The lowest risk of miscarriage (9.9%) was for women under 38 years of age, with primary infertility without a female cause and producing more than three oocytes. Although the analysis was performed only on stimulated IVF cycles (excluding unstimulated cycles), the data had the limitation that there was no information on the total gonadotrophin consumption. The model was adjusted for age and type of infertility, but the dataset contained no information on other confounders such as body mass index (BMI) of the women to allow adjustment. Analysis of this extensive dataset suggests that poor responders have a higher risk of clinical miscarriage, indicating that poor ovarian response is associated with a parallel decline in both oocyte quantity and quality. The miscarriage rate is also higher with advanced age, secondary infertility and a female cause of infertility compared with a younger age, male factor infertility and unexplained cause.

Effect of preovulatory progesterone elevation and duration of progesterone elevation on the pregnancy rate of frozen–thawed embryo transfer in natural cycles

To assess the incidence of P elevation (PE) in natural cycles and evaluate its effect on frozen-thawed embryo transfer cycles performed in natural cycles (FET-NC). Retrospective analysis. A tertiary assisted reproductive unit. Subfertile woman who did not conceive in their stimulated IVF cycle and underwent the first FET-NC cycle. Achieved serum samples were assayed for P concentrations from the day of LH surge up to 3 days before the surge. The cutoff level of PE was defined as 5 nmol/L. Clinical and ongoing pregnancy rates. The incidence of PE in natural cycles was 173 of 610 (28.4%). There were no significant differences in both clinical and ongoing pregnancy rates (39.0% vs. 37.3% and 32.5% vs. 31.7%) between those with vs. without PE on the day of LH surge. If PE lasted for 2 days or more, there was a significant reduction in the clinical pregnancy rate (39.4% vs. 20.7%). Using multivariate logistic regression, women's age, PE for 2 days or more, and the number of top-quality embryos were the significant factors for clinical pregnancy rates in FET-NC. The incidence of PE in FET-NC was similar to that in stimulated cycles. Progesterone elevation for 2 days or more before the LH surge impaired the clinical pregnancy rate of FET-NC, whereas PE on the day of LH surge only did not have such an adverse effect.

Anti-Müllerian hormone (AMH): a reliable biomarker of oocyte quality in IVF

To evaluate the impact of serum AMH levels on stimulated IVF implantation and clinical pregnancy rates. • Retrospective study with multivariate analysis. • Clinique ovo (Montreal University affiliated Center). • Six hundred and thirty seven patients undergoing a stimulated IVF protocol were included. Only non-polycystic ovary patients at their first IVF attempt were considered for the analysis. • None. • Implantation and ongoing pregnancy rates. Cycle outcomes were analysed according to AMH percentiles based on the AMH normogram per patient's age of our infertile population. Multivariate analyses were done to adjust for potential confounding factors such as age, total exogenous FSH dosage and number of eggs retrieved. Compared to the reference population, a significant lower mean implantation rate (0.26 vs 0.45) was observed in patients under 35 years of age with AMH < 1 ng/ml. Women with AMH < 25th percentile had less chances of having an embryo transferred, lower chances of having an ongoing pregnancy per started IVF cycle and a lower embryo freezing rate compared to the reference population. Patients with AMH < 0.47 ng/ml should be advised before starting a stimulated IVF cycle of the poorer prognosis compared to our reference population independently of their age, total exogenous FSH dosage and number of eggs retrieved. Therefore, AMH could enable a more individualized number of embryo transfer policy based on oocyte quality.

Should immature oocytes be routinely assessed for in vitro maturation and undergo ICSI during stimulated IVF cycles?

After oocyte denudation, some metaphase I (MI) oocytes may undergo spontaneous in vitro maturation to reach metaphase II (MII) before ICSI. This study aims to determine the fertilization and blastocyst rates of in vitro matured (Late MII) oocytes compared to in vivo matured sibling MII oocytes in IVF-ICSI cycles.

Oocyte telomere length is associated with ovarian reserve and ovarian response in female infertility patients

Aging reduces both oocyte quantity (ovarian reserve) and quality. As women are increasingly delaying childrearing, measures of oocyte quality are urgently needed. Telomeres mediate cellular aging and may mark oocyte quality (Kalmbach et al, F&S, 2013). Since oocyte quality generally declines with ovarian reserve, we tested the hypothesis that decreased oocyte telomere length would be associated with diminished ovarian reserve and response during stimulated IVF cycles.

Cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the Bologna criteria

Cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the Bologna criteria

Individualized decision-making in IVF: calculating the chances of pregnancy

Are we able to develop a model to calculate the chances of pregnancy prior to the start of the first IVF cycle as well as after one or more failed cycles? Our prediction model enables the accurate individualized calculation of the probability of an ongoing pregnancy with IVF. To improve counselling, patient selection and clinical decision-making in IVF, a number of prediction models have been developed. These models are of limited use as they were developed before current clinical and laboratory protocols were established. This was a cohort study. The development set included 2621 cycles in 1326 couples who had been treated with IVF or ICSI between January 2001 and July 2009. The validation set included additional data from 515 cycles in 440 couples treated between August 2009 and April 2011. The outcome of interest was an ongoing pregnancy after transfer of fresh or frozen-thawed embryos from the same stimulated IVF cycle. If a couple became pregnant after an IVF/ICSI cycle, the follow-up was at a gestational age of at least 11 weeks. Women treated with IVF or ICSI between January 2001 and April 2011 in a university hospital. IVF/ICSI cycles were excluded in the case of oocyte or embryo donation, surgically retrieved spermatozoa, patients positive for human immunodeficiency virus, modified natural IVF and cycles cancelled owing to poor ovarian stimulation, ovarian hyperstimulation syndrome or other unexpected medical or non-medical reasons. Thirteen variables were included in the final prediction model. For all cycles, these were female age, duration of subfertility, previous ongoing pregnancy, male subfertility, diminished ovarian reserve, endometriosis, basal FSH and number of failed IVF cycles. After the first cycle: fertilization, number of embryos, mean morphological score per Day 3 embryo, presence of 8-cell embryos on Day 3 and presence of morulae on Day 3 were also included. In validation, the model had moderate discriminative capacity (c-statistic 0.68, 95% confidence interval: 0.63-0.73) but calibrated well, with a range from 0.01 to 0.56 in calculated probabilities. In our study, the outcome of interest was ongoing pregnancy. Live birth may have been a more appropriate outcome, although only 1-2% of all ongoing pregnancies result in late miscarriage or stillbirth. The model was based on data from a single centre. The IVF model presented here is the first to calculate the chances of an ongoing pregnancy with IVF, both for the first cycle and after any number of failed cycles. The generalizability of the model to other clinics has to be evaluated more extensively in future studies (geographical validation). Centres with higher or lower success rates could use the model, after recalibration, by adjusting the intercept to reflect the IVF success rates in their centre. This project was funded by the NutsOhra foundation (Grant 1004-179). The NutsOhra foundation had no role in the development of our study, in the collection, analysis and interpretation of data; in writing of the manuscript, and in the decision to submit the manuscript for publication. There were no competing interests.