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Background: As women with low ovarian reserve embark on the challenging journey of in-vitro fertilisation (IVF) treatment, the choice between natural and mildly stimulated cycles becomes a pivotal consideration. It is unclear which of these two regimens is superior for women with low ovarian reserve. Our study aims to assess the impact of natural cycles on embryo quality and pregnancy outcomes in women with low ovarian reserve undergoing IVF treatment compared to mildly stimulated cycles. Methods: This retrospective study enrolled consecutive patients with low ovarian reserve who underwent IVF/intracytoplasmic sperm injection (ICSI) at Guangdong Second Provincial General Hospital between January 2017 and April 2021. The primary outcome for pregnancy rate of 478 natural cycles and 448 mild stimulated cycles was compared. Secondary outcomes included embryo quality and oocyte retrieval time of natural cycles. Results: The pregnancy rate in the natural cycle group was significantly higher than that in the mildly stimulated cycle group (51.8% vs. 40.1%, p = 0.046). Moreover, natural cycles exhibited higher rates of available embryos (84.1% vs. 78.6%, p = 0.040), high-quality embryos (61.8% vs. 53.2%, p = 0.008), and utilisation of oocytes (73% vs. 65%, p = 0.001) compared to mildly stimulated cycles. Oocyte retrievals in natural cycles were predominantly performed between 7:00 and 19:00, with 94.9% occurring during this time frame. In natural cycles with high-quality embryos, 96.4% of oocyte retrievals were also conducted between 7:00 and 19:00. Conclusion: Natural cycles with appropriately timed oocyte retrieval may present a valuable option for patients with low ovarian reserve. PLAIN LANGUAGE SUMMARY: In the realm of in-vitro fertilisation (IVF) treatment, women with low ovarian reserve often face the crucial decision of opting for natural or mildly stimulated cycles. This retrospective study, conducted between January 2017 and April 2021 at Guangdong Second Provincial General Hospital, delves into the impact of these cycles on pregnancy outcomes. Examining 478 natural cycles and 448 mildly stimulated cycles, the study reveals a notably higher pregnancy rate in the natural cycle group (51.8% vs. 40.1%). Additionally, natural cycles demonstrated higher rates of available embryos, high-quality embryos, and oocyte utilisation compared to their mildly stimulated counterparts. The findings suggest that natural cycles, with proper oocyte retrieval timing, could be a favourable choice for those with low ovarian reserve seeking IVF treatment. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there an increase in the total number of metaphase II (MII) oocytes between a conventional ovarian stimulation (OS) and a double uninterrupted stimulation? SUMMARY ANSWER There is no increase in the total number of MII oocytes when comparing one conventional OS to a continuous stimulation with double oocyte aspiration. WHAT IS KNOWN ALREADY Based on the concept of multiple follicular waves, the combination of two stimulations in the same ovarian cycle has gained interest in patients with a low ovarian reserve. This so-called dual stimulation approach is usually characterized by a discontinuation of FSH administration for ∼5 days and appears to have a favourable impact on the number of retrieved oocytes without affecting the embryo quality or ploidy status. The outcomes of dual uninterrupted OS have not yet been studied. STUDY DESIGN, SIZE, DURATION This was an open-label randomized controlled trial (RCT) with superiority design, performed in a single tertiary centre. Subjects were randomized with a 1:1 allocation into two groups between October 2019 and September 2021. All patients underwent a conventional stimulation with recombinant FSH. When two or more follicles of 17 mm were present, the final inclusion criterion was assessed; randomization occurred only in the presence of ≤9 follicles of ≥11 mm. In Group A, ovulation was triggered with hCG, and oocyte retrieval (OR) was performed 34–36 h later, followed by a fresh single or double embryo transfer (SET or DET) on Day 3/5. In Group B, ovulation was triggered with GnRH agonist, followed by another OS, without discontinuation of the FSH administration. In the presence of one or more follicles of ≥17 mm, the second stimulation was completed with hCG. A freeze-all strategy (Day 3/5) was applied for both retrievals, followed by transfer of one or two embryos in an artificially prepared frozen-thawed cycle. In the absence of one or more follicles of ≥17 mm after 13 additional days of stimulation, the second cycle was cancelled. All ORs were executed by a senior fertility specialist who was blinded for the first treatment, and all follicles >10 mm were aspirated, according to routine clinical practice. The primary outcome was the total number of MII oocytes. Patients were followed up until all embryos were transferred, or until live birth was achieved. Other secondary outcomes included the number of cumulus–oocyte complexes (COCs), the number of good quality embryos (Day 3/5), the ongoing pregnancy rate, and gonadotropin consumption. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients between 25 and 40 years old, with an anti-Müllerian hormone level of ≤1.5 ng/ml, antral follicle count of ≤6, or ≤5 oocytes after a previous stimulation, were included. At the start, 70 patients were eligible for participation in the trial, of whom 48 patients fulfilled the final inclusion criterium and were randomized. After drop-out of two patients, 23 patients were randomized to a single round of OS (Group A), and 23 patients were randomized to two uninterrupted rounds of OS (Group B). MAIN RESULTS AND THE ROLE OF CHANCE Baseline characteristics were similar between both groups. The cumulative number of COCs and MII oocytes after completion of the second OR was similar in Group A and Group B [5.3 ± 2.7 versus 5.3 ± 3.0 (P  = 0.95); 4.1 ± 2.4 versus 4.3 ± 2.7 (P  = 0.77)]. Likewise, a comparable number of excellent and good quality embryos was available on Day 3 (3.0 ± 2.0 versus 2.7 ± 2.0; P  = 0.63). In Group B, the cancellation rate due to insufficient response to the second round of stimulation was 39.1% (9/23). When focusing on the first stimulation in both groups, there were no significant differences regarding basal FSH, gonadotropin consumption, and the number of preovulatory follicles. After the first OR, the mean number of COC and MII oocytes was significantly higher in Group A (who had hCG triggering), compared to Group B (who had GnRH agonist triggering) [5.3 ± 2.7 versus 3.3 ± 2.2; difference 95% CI (0.54 to 3.45), P  = 0.004 and 4.1 ± 2.4 versus 3.0 ± 2.2; difference 95% CI (−0.15 to 2.6), P  = 0.05, respectively]. Likewise, the number of excellent and good quality embryos on Day 3 was significantly higher (3.0 ± 2.0 versus 1.9 ± 1.7; P  = 0.02) in Group A. LIMITATIONS, REASONS FOR CAUTION This study was powered to demonstrate superiority for the number of MII oocytes after dual stimulation. Investigating the impact of dual stimulation on pregnancy rates would have required a larger sample size. Furthermore, the heterogeneity in embryo vitrification and transfer policies precluded a correct comparison of embryologic outcomes between both groups. WIDER IMPLICATIONS OF THE FINDINGS This is the first RCT investigating the role of continuous stimulation with double aspiration in low responders. Our results show no statistically significant differences in the cumulative number of MII oocytes between one conventional stimulation with fresh ET and two consecutive stimulations with a freeze-only approach. Furthermore, the observed suboptimal oocyte yield after agonist ovulation triggering in low responders in the dual uninterrupted OS group is a reason for concern and further scrutiny, given that previous RCTs have shown similar outcomes in normal and high responders after hCG and GnRH agonist triggers. STUDY FUNDING/COMPETING INTEREST(S) This work was supported in part by a research grant from Organon. H.T. received honoraria for lectures and presentations from Abbott, Cooper Surgical, Gedeon-Richter, Cook, Goodlife, and Ferring. L.B. received fees for lectures from Merck & Organon and support for attending ESHRE 2023. M.D.V. reports fees for lectures from Ferring, Merck, Organon, IBSA, Gedeon Richter, and Cooper Surgical and support for attending ASRM 2023. S.M. received honoraria for lectures and presentations from Abbott, Cooper Surgical, Gedeon-Richter, IBSA, and Merck. C.B. was on the Advisory board and received consulting fees from Theramex and received honoraria for lectures and presentations from Abbott, Ferring, Gedeon-Richter, IBSA, and Merck. TRIAL REGISTRATION NUMBER NCT03846544 TRIAL REGISTRATION DATE 19 February 2019 DATE OF FIRST PATIENT'S ENROLMENT 28 October 2019 [ABSTRACT FROM AUTHOR]

Objective: To conduct a systematic examination and meta-analysis of the most reliable data from experimental studies evaluating the efficacy of autologous platelet-rich plasma (PRP) on low ovarian reserve. Methods: A comprehensive search was performed utilizing pertinent search terms across electronic databases, including PubMed, Cochrane, and Google Scholar. We included studies that assigned infertile women with low ovarian reserve in experimental studies. Ovarian reserve parameters were measured before and after PRP injection into ovaries. The data of each study was retrieved and subsequently compiled. Results: Of 301 articles collected and reviewed, six studies were finally included in the meta-analysis. Following PRP injection, infertile women showed a non-significant increase in anti-Mullerian hormone (AMH) level (MD=0.10; 95% CI -0.04, 0.23), a significant increase in antral follicular count (AFC) (MD=1.88; 95% CI 0.47, 3.29), and a non-significant reduction in follicle-stimulating hormone (FSH) level (MD=-0.22; 95% CI -8.32, 7.87). Conclusions: Autologous PRP may increase AFC, but not AMH. Although it is found beneficial in enhancing ovarian reserve (AFC), further research with strong evidence is still required.

STUDY QUESTION Does 8 weeks of daily low-dose hCG administration affect androgen or inhibin B levels in serum and/or follicular fluid (FF) during the subsequent IVF/ICSI cycle in women with low ovarian reserve? SUMMARY ANSWER Androgen levels in serum and FF, and inhibin B levels in serum, decreased following 8 weeks of hCG administration. WHAT IS KNOWN ALREADY Recently, we showed that 8 weeks of low-dose hCG priming, in between two IVF/ICSI treatments in women with poor ovarian responder (anti-Müllerian hormone (AMH) <6.29 pmol/l), resulted in more follicles of 2–5 mm and less of 6–10-mm diameter at the start of stimulation and more retrieved oocytes at oocyte retrieval. The duration of stimulation and total FSH consumption was increased in the IVF/ICSI cycle after priming. Hypothetically, hCG priming stimulates intraovarian androgen synthesis causing upregulation of FSH receptors (FSHR) on granulosa cells. It was therefore unexpected that antral follicles were smaller and the stimulation time longer after hCG priming. This might indicate a different mechanism of action than previously suggested. STUDY DESIGN, SIZE, DURATION Blood samples were drawn on stimulation day 1, stimulation days 5–6, trigger day, day of oocyte retrieval, and oocyte retrieval + 5 days in the IVF/ICSI cycles before and after hCG priming (the control and study cycles, respectively). FF was collected from the first aspirated follicle on both sides during oocyte retrieval in both cycles. The study was conducted as a prospective, paired, non-blinded, single-center study conducted between January 2021 and July 2021 at a tertiary care center. The 20 participants underwent two identical IVF/ICSI treatments: a control cycle including elective freezing of all blastocysts and a study cycle with fresh blastocyst transfer. The control and study cycles were separated by 8 weeks (two menstrual cycles) of hCG priming by daily injections of 260 IU recombinant hCG. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged 18–40 years with cycle lengths of 23–35 days and AMH <6.29 pmol/l were included. Control and study IVF/ICSI cycles were performed in a fixed GnRH-antagonist protocol. MAIN RESULTS AND THE ROLE OF CHANCE Inhibin B was lower on stimulation day 1 after hCG priming (P  = 0.05). Dehydroepiandrosterone sulfate (DHEAS) was significantly lower on stimulation day 1 (P  = 0.03), and DHEAS and androstenedione were significantly lower on stimulation days 5–6 after priming (P  = 0.02 and P  = 0.02) The testosterone level in FF was significantly lower in the study cycle (P  = 0.008), while the concentrations of inhibin B and androstenedione in the FF did not differ between the study and control cycles. A lower serum inhibin B in the study cycle corresponds with the antral follicles being significantly smaller after priming, and this probably led to a longer stimulation time in the study cycle. This contradicts the theory that hCG priming increases the intraovarian androgen level, which in turn causes more FSHR on developing (antral up to preovulatory) follicles. However, based on this study, we cannot rule out that an increased intra-follicular androgen level was present at initiation of the ovarian stimulation, without elevating the androgen level in serum and that an increased androgen level may have rescued some small antral follicles that would have otherwise undergone atresia by the end of the previous menstrual cycle. We retrieved significantly more oocytes in the Study cycle, and the production of estradiol per follicle ≥10-mm diameter on trigger day was comparable in the study and control cycles, suggesting that the rescued follicles were competent in terms of producing oocytes and steroid hormones. LIMITATIONS, REASONS FOR CAUTION The sample size was small, and the study was not randomized. Our study design did not allow for the measurement and comparison of androgen levels or FSHR expression in small antral follicles before and immediately after the hCG-priming period. WIDER IMPLICATIONS OF THE FINDINGS The results make us question the mechanism of action behind hCG priming prior to IVF. It is important to design a study with the puncture of small antral follicles before and immediately after priming to investigate the proposed hypothesis. Improved cycle outcomes, i.e. more retrieved oocytes, must be confirmed in a larger, preferably randomized study. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by an unrestricted grant from Gedeon Richter awarded to the institution. A.P. reports personal consulting fees from PregLem SA, Novo Nordisk A/S, Ferring Pharmaceuticals A/S, Gedeon Richter Nordics AB, Cryos International, and Merck A/S outside the submitted work and payment or honoraria for lectures from Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, Merck A/S, and Theramex and Organon & Co and payment for participation in an advisory board for Preglem. Grants to the institution have been provided by Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, and Merck A/S, and equipment and travel support has been given to the institution by Gedeon Richter Nordics AB. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Identifier: NCT04643925. [ABSTRACT FROM AUTHOR]

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STUDY QUESTION Does 8 weeks of continuous low-dose hCG administration increase the proportion of antral follicles that reach the preovulatory state during ovarian stimulation (OS) in women with low ovarian reserve? SUMMARY ANSWER The proportion of antral follicles (2–10 mm) that reached the preovulatory state did not increase. WHAT IS KNOWN ALREADY The administration of androgens prior to OS might upregulate FSH receptor (FSHR) expression on granulosa cells, making follicles more responsive to exogenous FSH stimulation during OS. LH and hCG stimulate the local follicular androgen synthesis in theca cells and may be used as an endogenous androgen priming method. Exogenous priming by testosterone and dehydroepiandrosterone (DHEA) have been shown to increase the number of retrieved oocytes and live birth rate but the studies are small, and their use is associated with side effects. STUDY DESIGN, SIZE, DURATION A prospective, paired, non-blinded single-center study including 20 women serving as their own controls conducted between January 2021 and July 2021 at The University Hospital Copenhagen Rigshospitalet, Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants underwent two identical consecutive IVF/ICSI treatments, a Control cycle and a Study cycle, separated by ∼8 weeks (two menstrual cycles) of daily injections of 260 IU recombinant hCG (rhCG). A freeze-all strategy was applied in the Control cycle. Both IVF/ICSI cycles were performed in a fixed GnRH antagonist protocol using a daily dose of 300 IU recombinant FSH (rFSH) and GnRH antagonist 0.25 mg from stimulation days 5–6. MAIN RESULTS AND THE ROLE OF CHANCE Follicular output rate, defined as the number of follicles >16 mm on hCG trigger day divided by the antral follicle count (2–10 mm) at baseline, did not increase after 8 weeks of hCG priming (P  = 0.8). The mean number of oocytes retrieved was significantly higher after the hCG priming being 4.7 (2.8) vs 3.2 (1.7) in the Study and Control cycle, respectively (P  = 0.01). The duration of stimulation was longer in the Study versus the Control cycle (P  = 0.05), despite the use of identical hCG trigger criterion and similar diameters of the three biggest follicles on hCG trigger day in the two cycles (P  = 0.9). LIMITATIONS, REASONS FOR CAUTION The sample size was small, and the number of oocytes retrieved was not the primary endpoint. Larger studies are needed to confirm this finding. WIDER IMPLICATIONS OF THE FINDINGS Long-term, low-dose rhCG administration may increase the number of oocytes retrieved during IVF/ICSI in women with low ovarian reserve, but more research is needed before firm conclusions can be drawn. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by an unrestricted grant from Gedeon Richter. A.P. reports personal consulting fees from PregLem SA, Novo Nordisk A/S, Ferring Pharmaceuticals A/S, Gedeon Richter Nordics AB, Cryos International, and Merck A/S outside the submitted work and payment or honoraria for lectures from Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, Merck A/S, and Theramex and Organon & Co. Grants to the institution have been provided by Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, and Merck A/S and receipt of equipment by the institution from Gedeon Richter Nordics AB is reported. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Identifier: NCT04643925. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to compare the elastographic properties of the ovaries of patients with poor ovarian response (POR) with healthy controls by using real-time ultrasound tissue elastography and to investigate the predictive value of ovarian strain ratio (OSR) in the diagnosis of POR., Materials and Methods: A cross-sectional study was conducted among infertility patients. OSR measurements of 46 women diagnosed with POR and 41 healthy controls with male infertility were performed by real-time ultrasound tissue elastography. Ovarian volume, OSR, antral follicle count (AFC), age, body mass index (BMI), anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), and estradiol (E2) values, were compared between the groups. A receiver operating characteristic curve was used to compare the sensitivity and specificity of OSR, AFC, AMH, FSH, and E2 for POR diagnosis., Results: Patients with POR were significantly older, had a lower duration of infertility, lower AMH, higher FSH, higher E2, lower AFC and ovarian volume (p < 0.01, p = 0.02, p < 0.01, p < 0.01, p < 0.01, p < 0.01, p < 0.01, respectively). The mean OSR of both ovaries was similar between the groups. For the diagnosis of POR, the sensitivity and specificity for AMH were 97.5% and 100%, for AFC were 86.7% and 97.6%; for FSH were 66.7% and 80.5%, for E2 were 53.3% and 90.2%, respectively., Conclusions: The significant independent predictors of the POR were AMH, AFC, and FSH, with no additional significant contribution from OSR. However, considering the relationship between POR and ovarian fibrosis, it is recommended to investigate this issue in more comprehensive studies., (© 2024 Wiley Periodicals LLC.)

Purpose: We sought to explore the utility of preimplantation genetic testing for aneuploidy (PGT-A) in a poor prognosis group of women with few embryos available for transfer. Methods: This was a retrospective matched cohort study examining records for first or second-cycle IVF patients with 1 to 3 blastocysts. The study group comprised 130 patients who underwent PGT-A on all embryos. The control group included 130 patients matched by age, BMI, and blastocyst number and quality who did not undergo PGT-A during the same time period. Results: The live birth rate (LBR) per embryo transfer (ET) were similar in the PGT-A and control groups, and the spontaneous abortion (SAB) rate was the same (23%). However, we found a significantly higher LBR per oocyte retrieval in the control group vs the PGT-A group (43% vs 20%, respectively) likely due to the many no-euploid cycles in the PGT-A group. In a subgroup analysis for age, the similar LBR per ET persisted in women < 38. However, in older women, there was a trend to a higher LBR per ET in the PGT-A group (43%) vs the control group (22%) but a higher LBR per oocyte retrieval in the control group (31%) vs the PGT-A group (13%). Conclusions: Overall, we observed a significant increase in LBR per oocyte retrieval in women in the control group compared to women undergoing PGT-A, and no difference in SAB rate. Our data suggests that PGT-A has no benefit in a subpopulation of women with few embryos and may cause harm. [ABSTRACT FROM AUTHOR]

Several chemical, mechanical, or physical stimuli can be used to promote oocyte activation during ICSI cycles. Calcium ionophore is the most commun method for chemical oocyte activation and activation may be beneficial for cases of globozoospermia, low oocyte count, total fertilization failure, recurrent implantation failure (1,2). In what concern low ovarian reserve cases, a subgroup of infertile couples with relatively poor prognosis, artificial oocyte activation with calcium ionophore may improve fertilization rates, embryo number, embryo quality and pregnancy rates. This study aimed to find out whether Ca2+ ionophore improves fertilization, embryo development and pregnancy out comes in patients with low ovarian reserve. This study is conducted at Istanbul University, Istanbul Faculty of Medicine, Department of Obstetrics and Gynecology, Reproductive Endocrinology and Infertility Unit. All IVF-ICSI cycles performed because of female factor, low ovarian reserve between November 2023 and July 2024 are included.Patients with DOR indication, who were administered calcium ionophore(GROUP I/Experimental Group, n:30) and patients who were not administered calcium ionophore (GROUP II/Control Group, n:30) were included. These patients were compared in terms of fertilization, embryo quality and pregnancy rates.Oocytes at the MII stage obtained from patients were subjected to ICSI approximately 4 hours after oocyte retrieval(OPU). After ICSI, the oocytes were incubated in a calcium ionophore solution for 20 minutes and then transferred to culture media. On the following days, fertilization rates, embryo development, and pregnancy statuses were assessed. The results were statistically evaluated using independent samples t-test and chi-square test. Statistical significance was considered as p<0.05 No differences were observed between the two groups in terms of female age, BMI, duration of infertility, AMH, FSH, LH, estradiol, oocyte count, oocyte maturation, and fertilization rate factors.However, the transfer of medium-quality embryos was found to be significantly higher in the DOR group without calcium ionophore application(p=0.035).The number of embryos frozen in Group I was significantly higher compared to Group II (p=0.020) (Table).No significant difference was found between the two groups in terms of clinical pregnancy and ongoing pregnancy rates. Alternative laboratory treatments applied to patients with low ovarian reserve may yield positive results in terms of increasing the likelihood of success. Our study has shown that the application of calcium ionophore in these cases leads to better-quality embryo development and consequently an increased number of frozen embryos. Although no significant difference was observed in clinical pregnancy and ongoing pregnancy rates, increasing the number of patients in the study could yield more definitive results. [ABSTRACT FROM AUTHOR]

Abstract Previously anecdotally observed rebounds in follicle growth after interruption of exogenous gonadotropins in absolute non-responders were the impetus for here reported study. In a prospective cohort study, we investigated 49 consecutive patients, absolutely unresponsive to maximal exogenous gonadotropin stimulation, for a so-called rebound response to ovarian stimulation. A rebound response was defined as follicle growth following complete withdrawal of exogenous gonadotropin stimulation after complete failure to respond to maximal gonadotropin stimulation over up to 5–7 days. Median age of study patients was 40.5 ± 5.1 years (range 23–52). Women with and without rebound did not differ significantly (40.0 ± 6.0 vs. 41.0 ± 7.0 years, P = 0.41), with 24 (49.0%) recording a rebound and 25 (51.0%) not. Among the former, 21 (87.5%) reached retrieval of 1–3 oocytes and 15 (30.6%) reached embryo transfer. A successful rebound in almost half of prior non-responders was an unsuspected response rate, as was retrieval of 1–3 oocytes in over half of rebounding patients. Attempting rebounds may, thus, represent another incremental step in very poor prognosis patients before giving up on utilization of autologous oocytes. Here presented findings support further investigations into the underlying physiology leading to such an unexpectedly high rebound rate.

Objective: To investigate whether ovarian fragmentation for follicular activation (OFFA) improves ovarian reserve markers and in vitro fertilization (IVF) outcomes in women with poor ovarian response (POR).Design: Randomized, controlled trial, with parallel assignment.Setting: University hospital.Patient(s): Thirty-four women with POR according to the European Society of Human Reproduction and Embryology criteria.Intervention(s): Women with POR were randomly allocated to receive ovarian fragmentation in 1 ovary or to no intervention (control group). Ovarian reserve markers were followed at 2-week intervals for 6 months. In vitro fertilization cycles were initiated when the antral follicle count (AFC) doubled or at the end of follow-up.Main Outcome Measure(s): The primary outcome was the number of metaphase II (MII) oocytes obtained. Antral follicle count, antimüllerian hormone level, and reproductive outcomes were recorded as secondary outcomes. Exploratory outcomes included surgical results and analysis of protein and gene expression.Result(s): Ovarian fragmentation for follicular activation resulted in an increase in AFC in the intervention ovary compared with the control ovary and an increase in total AFC in the OFFA group compared with controls. Serum antimüllerian hormone and follicle-stimulating-hormone levels did not improve in the OFFA group throughout the follow-up period. Fifteen patients from each arm underwent IVF. In the control group, 33 MII oocytes were retrieved and 18 embryo transfers were performed, with a 20% pregnancy rate and an 18.7% live birth rate per cycle. In the OFFA group, 23 MII oocytes were retrieved and 11 embryo transfers were performed, with a 13.3% pregnancy rate and a 6.7% live birth rate per cycle. Reproductive outcomes did not significantly differ between the groups. Hippo pathway inhibition was confirmed by an 18.8% reduction in the phospho-YAP/YAP (Yes-associated protein 1) ratio and BIRC and CCN overexpression after fragmentation.Conclusion(s): Ovarian fragmentation for follicular activation in women with POR resulted in an increase in AFC but did not modify IVF outcomes when compared with controls.Clinical Trial Registration Number: NCT02354963. [ABSTRACT FROM AUTHOR]

Background: Mild ovarian stimulation has emerged as an alternative to conventional IVF with the advantages of being more patient-friendly and less expensive. Inadequate data on pregnancy outcomes and concerns about the cycle cancellation rate (CCR) have prevented mild, or low-dose, IVF from gaining wide acceptance.Objective and Rationale: To evaluate parallel-group randomised controlled trials (RCTs) on IVF where comparisons were made between a mild (≤150 IU daily dose) and conventional stimulation in terms of clinical outcomes and cost-effectiveness in patients described as poor, normal and non-polycystic ovary syndrome (PCOS) hyper-responders to IVF.Search Methods: Searches with no language restrictions were performed using Medline, Embase, Cochrane central, Pre-Medicine from January 1990 until April 2020, using pre-specified search terms. References of included studies were hand-searched as well as advance access articles to key journals. Only parallel-group RCTs that used ≤150 IU daily dose of gonadotrophin as mild-dose IVF (MD-IVF) and compared with a higher conventional dose (CD-IVF) were included. Studies were grouped under poor, normal or hyper-responders as described by the authors in their inclusion criteria. Women with PCOS were excluded in the hyper-responder group. The risk of bias was assessed as per Cochrane Handbook for the included studies. The quality of evidence (QoE) was assessed according to the GRADE system. PRISMA guidance was followed for review methodology.Outcomes: A total of 31 RCTs were included in the analysis: 15 in the poor, 14 in the normal and 2 in the hyper-responder group. Live birth rates (LBRs) per randomisation were similar following use of MD-IVF in poor (relative risk (RR) 0.91 (CI 0.68, 1.22)), normal (RR 0.88 (CI 0.69, 1.12)) and hyper-responders (RR 0.98 (CI 0.79, 1.22)) when compared to CD-IVF. QoE was moderate. Cumulative LBRs (5 RCTs, n = 2037) also were similar in all three patient types (RR 0.96 (CI 0.86 1.07) (moderate QoE). Risk of ovarian hyperstimulation syndrome was significantly less with MD-IVF than CD-IVF in both normal (RR 0.22 (CI 0.10, 0.50)) and hyper-responders (RR 0.47 (CI 0.31, 0.72)), with moderate QoE. The CCRs were comparable in poor (RR 1.33 (CI 0.96, 1.85)) and hyper-responders (RR 1.31 (CI 0.98, 1.77)) but increased with MD-IVF among normal responders (RR 2.08 (CI 1.38, 3.14)); all low to very low QoE. Although fewer oocytes were retrieved and fewer embryos created with MD-IVF, the proportion of high-grade embryos was similar in all three population types (low QoE). Compared to CD-IVF, MD-IVF was associated with less gonadotrophin use and lower cost.Wider Implications: This updated review provides reassurance on using MD-IVF not only for the LBR per cycle but also for the cumulative LBR, with moderate QoE. With risks identified with 'freeze-all' strategies, it may be time to recommend mild-dose ovarian stimulation for IVF for all categories of women i.e. hyper, poor and normal responders to IVF. [ABSTRACT FROM AUTHOR]

Previously anecdotally observed rebounds in follicle growth after interruption of exogenous gonadotropins in absolute non-responders were the impetus for here reported study. In a prospective cohort study, we investigated 49 consecutive patients, absolutely unresponsive to maximal exogenous gonadotropin stimulation, for a so-called rebound response to ovarian stimulation. A rebound response was defined as follicle growth following complete withdrawal of exogenous gonadotropin stimulation after complete failure to respond to maximal gonadotropin stimulation over up to 5–7 days. Median age of study patients was 40.5 ± 5.1 years (range 23–52). Women with and without rebound did not differ significantly (40.0 ± 6.0 vs. 41.0 ± 7.0 years, P = 0.41), with 24 (49.0%) recording a rebound and 25 (51.0%) not. Among the former, 21 (87.5%) reached retrieval of 1–3 oocytes and 15 (30.6%) reached embryo transfer. A successful rebound in almost half of prior non-responders was an unsuspected response rate, as was retrieval of 1–3 oocytes in over half of rebounding patients. Attempting rebounds may, thus, represent another incremental step in very poor prognosis patients before giving up on utilization of autologous oocytes. Here presented findings support further investigations into the underlying physiology leading to such an unexpectedly high rebound rate. [ABSTRACT FROM AUTHOR]

Due to the fact that modern American and European women postpone childbirth until later in life, they are more likely to face the problem of ovarian insufficiency by the time they are ready to have children. So, the ability to restore the ovarian function safely is crucially important. Our study involved 38 women 31–45 years of age with low ovarian reserves and at least two unsuccessful attempts to receive their oocytes through IVF. The blood from the patients was collected into two BD vacutainers for PRP preparation. The platelet concentration in the PRP was 1 × 106 μl. PRP injections into the ovaries were performed by a gynecologist with a special 25G needle, 20 cm in length, as an ultrasound-guided procedure or a laparoscopic-assisted approach. After PRP treatment, women were tested with several criteria for 12 months. We saw a significant improvement in hormone levels; six healthy babies were born, ten pregnancies were achieved, and four out of the ten were from natural conception. The PRP injections into the ovaries are safe, productive, and a natural treatment that may help women with premature ovarian insufficiency to give birth to their own child. The difference and novelty with our method of ovarian rejuvenation is in obtaining a higher platelet concentration (about 1 × 106 μl), which allows us to achieve long-lasting results, within 12 months, after a single procedure. Additionally, for the first time, we proposed and successfully performed a laparoscopically assisted technique for administering PRP into the ovary. [ABSTRACT FROM AUTHOR]

Premature ovarian failure (POF) is used to describe women under 40 years old with amenorrhea, hypergonadotropic hypogonadism, and infertility as a result of cessation of ovarian function. It has been reported that almost 20% of women who consult for infertility have signs of premature ovarian ageing. The mitochondrial disorder is one of the critical agents in premature menopause and the occurrence of POF Due to the maternal inheritance of POF along with the dependence of folliculogenesis upon the mitochondrial biogenesis and bioenergetics, it has been suggested that a generalized mitochondrial defect is likely involved in POF. A fuller understanding of the mitochondrial role in POF could contribute to the better management of women with POF in the future. The aim of this review was to illustrate the role of mitochondria in POF. The oocyte mitochondrial DNA (mtDNA) content in women with diminished ovarian reserve is significantly lower than women with normal ovarian reserve. It has been evidenced that mitochondrial genetic disorders and mitochondrial oxidative stress are associated with POF. According to the maternal inheritance of mtDNA, genetic testing should be performed to detect mtDNA mutations involved in POF before starting treatment strategies. If these mutations are present, it could suggest that healthy mitochondrial transfer during assisted reproductive technology should be used to prevent the transmission of POF caused by mtDNA mutation to the female offspring. Future strategies aimed at treatment of POF-related infertility should take into account the significance of the oocyte mitochondrial role in the occurrence of this disorder. [ABSTRACT FROM AUTHOR]

The pathophysiology of the genuine empty follicle syndrome (EFS) is still debated. Ovarian aging has been contested as a cause of this condition. Our aim was to investigate the occurrence of the genuine EFS in cases of a low number of mature follicles in a prospective manner. Ninety-five infertile women were recruited and evaluated following conventional controlled ovarian stimulation (COS) with ≤ six follicles of ≥14 mm diameter on the day of hCG administration. Enrolled women were 37.5 ± 5.2 years of age with basal FSH level of 9.1 ± 3.7 mIU/L, antral follicle count (AFC) of 6.9 ± 4.6, and number of ≥14 mm follicles (on the day of hCG) of 3.4 ± 1.5. Among the 95 women, four were complicated by the genuine EFS (4.2%) with features of the depleted ovarian reserve. Comparison between these four cases and the 91 controls revealed significant differences between age, AFC, number of ≥14 mm follicles, and serum E2 level corresponding to 41.8 ± 1.7 versus 37.4 ± 5.2 years, 1.7 ± 0.6 versus 7.1 ± 4.5, 2.0 ± 0.8 versus 3.4 ± 1.5 follicles, and 356 ± 200 versus 975 ± 557 pg/mL, respectively. Post hoc analysis revealed that 56 among the 95 women fulfilled the Bologna criteria for poor ovarian response and all four cases matched the definition of the genuine EFS raising its incidence to 7.1% in this group. A logistic regression analysis showed that AFC was a significant factor in the development of the genuine EFS. We conclude that the genuine EFS complicates infertile women characterized by a low number of mature follicles. Our findings suggest that the mechanism behind this occurrence is associated with a more exhausted ovarian reserve. [ABSTRACT FROM AUTHOR]

Key content: Early ovarian ageing (EOA) affects around 10% of women.Women with early ovarian ageing are frequently asymptomatic with normal fertility; however, continuing follicular loss will result in loss of fertility, menstrual irregularity and, finally, early menopause.As women increasingly delay childbirth, the physical, psychological and financial impact of EOA is escalating.Long‐term health effects include early menopause and increased cardiovascular risk.Improvements in the success of oocyte freezing have provided a treatment option when EOA is identified early. Learning objectives: To understand the prevalence and pathophysiology of EOA.To appreciate the effects of EOA on fertility, miscarriage risk and long‐term health.To be able to counsel women presenting with EOA regarding their fertility options. Ethical issues: Should women be screened for EOA?What is the efficacy of egg freezing for fertility preservation? [ABSTRACT FROM AUTHOR]

The purpose of this study is to determine whether all-blastocyst-culture can benefit advanced maternal age (AMA) patients with low ovarian reserve. We retrospectively analyze AMA patients with low ovarian reserve undergoing IVF/ICSI in Reproductive Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University from May 2016 to August 2017. We divide them into group A (all-blastocyst-culture) and group B (none-blastocystculture) based on different culture approach of D3 transferrable embryo. We compared the cumulative biochemical pregnancy rate and cumulative clinical pregnancy rate between them. A total of 261 eligible patients are included, with 151 in group A and 110 in group B. The basic conditions of the two groups show no difference. Cumulative biochemical pregnancy rate/clinical pregnancy rate in group A is higher than that of group B, though not statistically significant (p > .05). After removing patients canceling embryo transfer due to failure in blastocyst culture, the cumulative biochemical pregnancy rate/clinical pregnancy rate in group A is significantly higher than group B (p < .05). Multivariate analysis showed that female age and the number of D3 transferrable embryo are risk factors for the failure of blastocyst culture (OR = 0.672 and 2.270, 95%CI 0.511-0.883 and 1.203-4.284, p = .004 and p = .011, respectively). Hence, we drew to conclusion that all-blastocyst-culture will not adversely affect the pregnancy outcome of AMA patients with low ovarian reserve. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ovarian stimulation protocol and other potential risk factors of poor ovarian response (POR) were analyzed in retrospective case-control study. Due to ESHRE criteria (2011) 150 infertile women of IVF department were divided into the group of cases with POR and the control group with the normal ovarian response. The elder age of the women and the earlier age of menopause in their mothers seemed to be the significant risk factors of POR. Also POR was associated with the history of abortions, ovarian stimulation, and hormonal contraception. Ovarian stimulation protocol did not influence the number of follicles and oocytes in both case and control groups. The pregnancy rate was higher in patients with GnRH antagonists protocol.

Objective: To evaluate the effect of DHEA supplementation on In-Vitro Fertilisation (IVF) outcome as assessed by ovarian response, oocyte developmental competence and live birth rates in women predicted to have poor ovarian reserve (OR). The feasibility of conducting a large trial is also assessed by evaluating the recruitment rates and compliance of the recruited participants with DHEA/placebo intake and follow-up rates.Study Design: A single centre, double blinded, placebo controlled, randomized trial was performed over two years with 60 women undergoing in-vitro fertilisation (IVF). Subjects were randomized, based on a computer-generated pseudo-random code to receive either DHEA or placebo with both capsules having similar colour, size and appearance. 60 women with poor OR based on antral follicle count or anti-Mullerian hormone thresholds undergoing IVF were recruited. They were randomised to receive DHEA 75mg/day or placebo for at-least 12 weeks before starting ovarian stimulation. They had long protocol using hMG 300 IU/day. Data analysed by "intention to treat". Ovarian response, live birth rates and molecular markers of oocyte quality were compared between the study and control groups.Results: The recruitment rate was 39% (60/154). A total of 52 participants (27 versus 25 in the study and placebo groups) were included in the final analysis after excluding eight. While the mean (standard deviation) DHEA levels were similar at recruitment (9.4 (5) versus 7.5 (2.4) ng/ml; P=0.1), the DHEA levels at pre-stimulation were higher in the study group than in the controls (16.3 (5.8) versus 11.1 (4.5) ng/ml; P<0.01). The number (median, range) of oocytes retrieved (4, 0-18 versus 4, 0-15 respectively; P=0.54) and live birth rates (7/27, 26% versus 8/25, 32% respectively; RR (95% CI): 0.74 (0.22-2.48) and mRNA expression of developmental biomarkers in granulosa and cumulus cells were similar between the groups.Conclusion: Pre-treatment DHEA supplementation, albeit statistical power in this study is low, did not improve the response to controlled ovarian hyperstimulation or oocyte quality or live birth rates during IVF treatment with long protocol in women predicted to have poor OR. [ABSTRACT FROM AUTHOR]

Objectives: Platelet-rich plasma (PRP) is obtained by centrifuging the platelet-rich portion of the patient's own blood. The objective of our study is to retrospectively examine the impact of intraovarian PRP injection on infertile women with diminished ovarian reserve, specifically focusing on the oocyte count, oocyte quality, and endometrial thinning., Methods: A retrospective assessment was conducted on cases who had intraovarian PRP injection at the in vitro fertilization (IVF) unit of the Obstetrics and Gynecology Department of Gazi University School of Medicine hospital. The review encompasses the period from 1 January 2015 to 30 June 2020. The endometrial thickness, follicle count of greater than 14 millimeters, estradiol levels, follicle-stimulating hormone (FSH) levels, and antral follicle count were assessed during the menstrual cycle both prior to and within a period of 1-6 months following the PRP procedure. Twenty nonpregnant patients who had IVF before and 4-6 months after PRP were admitted to the post-PRP IVF cycle. The quantification of oocytes and M2 oocytes was conducted both prior to and subsequent to PRP treatment., Results: Among 120 cases, only 60 cases who fulfilled inclusion criteria were analyzed. The basal endometrial thickness, basal follicle number (>14 mm), estradiol value, oocyte count, and M2 oocyte count exhibited a statistically significant increase following the administration of PRP injection (p<0.001). The basal FSH value exhibited a notable drop following the administration of PRP injection, with a statistically significant difference (p=0.002). In the pregnant group, the number of oocytes obtained with oocyte pick-up (OPU) increased by 300%, and in the nonpregnant group, the increase was 125% only. The number of M2 oocytes obtained with OPU increased by 250% in the pregnant group, while it was 93% in the nonpregnant group., Conclusion: Ultimately, the affordability of PRP production and its considerable theoretical efficacy have the potential to substantially decrease the expenses associated with assisted reproductive technology procedures. In the present scenario, the administration of an intraovarian PRP injection may be contemplated as a therapeutic intervention for women exhibiting diminished ovarian reserve., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Safarova et al.)

Late follicular progesterone (P) elevation continues to complicate a significant part of assisted reproductive technologies (ART) cycles, despite the ardent employment of gonadotropin releasing hormone (GnRH) analogues. In women with good ovarian reserve, late follicular P elevation is believed to be the result of the controlled ovarian stimulation (COS) itself, multiple follicular development and excessive ovarian steroidogenic activity. These mechanisms do not seem to be plausible in women with low ovarian reserve. In these women, excessive COS achieve a small number of pre-ovulatory follicles, which is not coupled to considerable ovarian steroidogenic activity. Therefore, other mechanisms should be pursued and explored. Delicate paracrine and autocrine mechanisms within the oocyte-cumulus complex were suggested to preserve the integrity of the pre-ovulatory follicle, including inhibition of P increase and follicular luteinization. However, clinical studies to demonstrate the disruption of these mechanisms in cases with low ovarian reserve and ageing oocytes are still lacking. Late follicular progesterone/estradiol (P/E2) ratio was introduced into clinical practice as a more appropriate way to analyze P rise in women undergoing COS to control for the E2 increase. The current hypothesis claims that in a follicular environment were the mechanism that prevent premature luteinization is disrupted, independent to LH surge; P rise at the late follicular phase may relatively bypass normal E2 production, at the pre-ovulatory stage of steroidogenesis, causing a rise in the P/E2 ratio. Therefore, in women with low ovarian reserve and few pre-ovulatory follicles, undergoing conventional COS, a negative (reverse) correlation between number of maturing follicles and P/E2 ratio may support the existence of such a mechanism as its disruption, while a no or a positive correlation may disapprove it. [ABSTRACT FROM AUTHOR]

Study Question: Do infertile patients below the age of 40 years have a lower ovarian reserve, estimated by anti-Müllerian hormone (AMH) and total antral follicle count (AFC), than women of the same age with no history of infertility? Summary Answer: Serum AMH and AFC were not lower in infertile patients aged 20-39 years compared with a control group of the same age with no history of infertility. WHAT IS KNOWN ALREADY?: The management of patients with a low ovarian reserve and a poor response to controlled ovarian stimulation (COS) remains a challenge in assisted reproductive technologies (ART). Both AMH levels and AFC reflect the ovarian reserve and are valuable predictors of the ovarian response to exogenous gonadotrophins. However, there is a large inter-individual variation in the age-related depletion of the ovarian reserve and a broad variability in the levels of AMH and AFC compatible with conception. Women with an early depletion of the ovarian reserve may experience infertility as a consequence of postponement of childbearing. Thus, low ovarian reserve is considered to be overrepresented among infertile patients. Study Design, Size, Duration: A prospective cohort study including 382 women with a male partner referred to fertility treatment at Rigshospitalet, Copenhagen, Denmark during 2011-2013 compared with a control group of 350 non-users of hormonal contraception with no history of infertility recruited during 2008-2010. Participants/materials, Setting, Methods: Included patients and controls were aged 20-39 years. Women with polycystic ovary syndrome were excluded. On Cycle Days 2-5, AFC and ovarian volume were measured by transvaginal sonography, and serum levels of AMH, FSH and LH were assessed. Main Results and the Role Of Chance: Infertile patients had similar AMH levels (11%, 95% confidence interval (CI): -1;24%) and AFC (1%, 95% CI: -7;8%) compared with controls with no history of infertility in an age-adjusted linear regression analysis. The prevalence of very low AMH levels (<5 pmol/l) was similar in the two cohorts (age-adjusted odds ratio: 0.9, 95% CI: 0.5;1.7). The findings persisted after adjustment for smoking status, body mass index, gestational age at birth, previous conception and chronic disease in addition to age. Limitations, Reason For Caution: The comparison of ovarian reserve parameters in women recruited at different time intervals could be a reason for caution. However, all women were examined at the same centre using the same sonographic algorithm and AMH immunoassay. Wider Implications Of the Findings: This study indicates that the frequent observation of patients with a poor response to COS in ART may not be due to an overrepresentation of women with an early depletion of the ovarian reserve but rather a result of the expected age-related decline in fertility. Study Funding/competing Interests: The study received funding from MSD and the Interregional European Union (EU) projects 'ReproSund' and 'ReproHigh'. The authors have no conflict of interest. Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the concentrations of oxidative stress markers, antioxidant enzymes and cytokines in the follicular fluid of young women with low response in ovarian stimulation cycles compared with high responders and fertile oocyte donors of the same age, to assess the impact of oxidative stress on ovarian reserve. The activity of follicular fluid antioxidant enzymes glutathione transferase, glutathione reductase and glutathione peroxidase was significantly lower in young women with reduced ovarian reserve compared with that in high responders and oocyte donors. Follicular fluid concentrations of oxidative stress marker malondialdehyde combined with 4-hydroxyalkenals and nitric oxide were higher in low responders than in high responders and oocyte donors. Significant differences between low responders and donors in concentrations of IL-2, IL-6, IL-8 and vascular endothelial growth factor were observed, with higher concentrations in low responders. However, IL-10 concentration was lower in low responders than in high responders and donors. No significant differences were found in follicular fluid concentrations of tumour necrosis factor alpha between the three groups. These results demonstrate that different concentrations of oxidative stress markers, oxidant enzymes and cytokines in low responders compared with high responders and oocyte donors may negatively impact ovarian response. [ABSTRACT FROM AUTHOR]

Postponement of child bearing and maternal age at first pregnancy are on the rise, contributing considerably to an increase in age-related infertility and the demand for assisted reproductive technologies (ART) treatment. This brings to the infertility clinics many women with low ovarian reserve and poor ovarian response (POR) to conventional stimulation. The Bologna criteria were released to standardize the definition of POR and pave the way for the formulation of evidence-based, efficient modalities of treatment for women undergoing IVFET. More than four years have passed since the introduction of these criteria and the debate is still ongoing whether a revision is due. Women with POR comprise several sub-groups with diverse baseline distinctiveness, a major issue that has fueled the discussion. Although antral follicle count (AFC) and anti-Müllerian hormone (AMH), are considered good predictors of ovarian reserve, their threshold values are still not universally standardized. Different definitions for sonographic AFC and diverse assays for AMH are held responsible for this delay in standardization. Adding established risk factors to the criteria will lead to more reliable and reproducible definition of a POR, especially in young women. The original criteria did not address the issue of oocyte quality, and the addition of risk factors may yield specific associations with quality vs. quantity. Patient's age is the best available criterion, although limited, to predict live-birth and presumably oocyte quality. High scale studies to validate these criteria are still missing while recent evidence raises concern regarding over diagnosis. [ABSTRACT FROM AUTHOR]

At present, there are no proven therapies to improve ovarian function in women with premature ovarian insufficiency (POI) or in those with extremely low ovarian reserve (LOR). We report successful IVF outcomes achieved with continuous high-dose estrogen supplementation in patients with LOR. Patients were 33- and 42-year-old nulligravidae with high-serum FSH (over 30 IU/L) and undetectable serum AMH (under 0.1 ng/mL) levels; however, neither patient fulfilled the diagnostic criteria for POI. After cycle cancellation and unsuccessful IVF treatment, both patients received conjugated estrogen (CE) supplementation (2.5-3.75 mg/day) from day 2 of their menstrual cycle to the day of HCG administration in their IVF treatment cycles. Following continuous high-dose estrogen supplementation, oocytes were successfully retrieved from both patients and fertilized. Both patients also achieved ongoing pregnancy through frozen-thawed embryo transfer cycles. In conclusion, high-dose estrogen supplementation down-regulated serum FSH and LH within their physiological ranges, which led to functional follicle growth and prevented early luteinization. Further studies will be needed to confirm the effect of this treatment on POI patients and to establish a new and individualized protocol for LOR patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine whether the decrease in AMH levels during ovarian hyperstimulation for IVF occurs in patients with polycystic ovary syndrome (PCOS) and patients with low ovarian reserve (LOR), as in normal cycling women. Study design: A cohort of 22 infertile patients treated in a single tertiary center with a GnRH-antagonist short protocol for IVF were prospectively included and divided into three groups: PCOS with hyperandrogenism (n =7), LOR (n =8) and control (n =7). Serum AMH levels were measured before and during FSH treatment, on the day of HCG administration, at the mid-luteal phase, and 14 days after embryo transfer. The three groups were compared using an ANOVA model in the case of continuous data and with Fisher's exact test when the data were discrete. Results: In the PCOS group, AMH levels increased at the beginning of the stimulation, but later decreased, until the mid-luteal stage. In the other two groups, AMH levels decreased throughout ovarian stimulation until the mid-luteal stage. In all groups, AMH levels returned to baseline levels two weeks after HCG administration, regardless of treatment outcome (pregnancy or not). Conclusions: AMH levels decline during controlled ovarian hyperstimulation with a GnRH-antagonist short protocol in women with low and normal ovarian reserves. In contrast, in women with PCOS, an increase in AMH levels precedes this decline. These findings may support the hypothesis that androgens may play a role in AMH regulation in women. [Copyright &y& Elsevier]

Abstract: Objective: To investigate the association between thrombophilic risk factors and poor ovarian response in an assisted reproductive technologies (ART) setting. Study design: This is a preliminary prospective cohort study in a university affiliated reproductive medicine unit. Eighty-nine infertile women undergoing IVF-ET treatment were recruited. Following IVF-ET treatment, the 28 women that had ≤3 oocytes on retrieval were the study group, and the 61women that had ≥ 4 oocytes on retrieval were the control group. All women underwent ovarian reserve testing and thrombophilia work-up prior to treatment. Results: Patients’ characteristics, except for chronological age, were similar between the two groups. Women in the study group had clear manifestations of low ovarian reserve, evident by ovarian reserve testing, controlled ovarian hyper-stimulation and IVF-ET treatment results, as compared to the control group. The incidence of all thrombophilias tested was similar between the study and control group. Moreover, the incidence of any single or combined thrombophilia was also similar between the two groups. Logistic regression model analysis and Pearson correlation tests did not show significant correlation between number of oocytes retrieved and thrombophilia. Furthermore, basal ovarian reserve tests did not differ between women with and without thrombophilia. When only the 48 women ≤ 35 years of were analyzed, the five women in the study group had significantly higher incidence of a single as well as combined thrombophilia as compared to the 43 controls. Conclusions: Thrombophilic risk factors have no correlation with poor ovarian response in the general infertile population undergoing ART. Whether premature low ovarian reserve is linked to thrombophilia remains to be established. [Copyright &y& Elsevier]

In this retrospective study of 652 anticipated low response women, the overall clinical outcomes (live birth rate and clinical pregnancy rate [PR]) of low-dose flare (LDF) protocol appeared lower than those of conventional down-regulation (DR) (LDF: 15.1% vs. DR: 20.6% and LDF: 10.3% vs. DR: 17.4%, respectively). The findings that LDF protocol improved the clinical outcome in older women, or when LDF followed an unsuccessful IVF/intracytoplasmic sperm injection (ICSI) cycle with DR (LDF: 19.4% vs. DR: 9.76% and LDF: 13.9% vs. DR: 4.2% respectively), need further evaluation through randomized trials. [ABSTRACT FROM AUTHOR]

Objective: To find a simple multivariate score that has the potential to predict ovarian reserve, as well as pregnancy rate, in infertile women. Design: A prospective study. Setting: A university-affiliated reproductive medicine unit. Patient(s): One hundred sixty-eight consecutive women undergoing their first IVF-ET treatment at our unit. Intervention(s): Basal ovarian reserve studies, endocrine and sonographic, were performed before starting therapy. After completion of treatment, a logistic regression analysis was performed to examine which parameters significantly determined low ovarian reserve. These parameters were incorporated thereafter in a multivariate score to predict ovarian reserve, as well as clinical pregnancy rate. Main Outcome Measure(s): Low ovarian reserve defined as Result(s): Logistic regression analysis revealed that age, antral follicle count, basal FSH, FSH/LH ratio, mean ovarian volume, infertility duration, number of previous cycle cancellations, and body mass index were all, in decreasing significance, independent factors that determine low ovarian reserve. The multivariate score was shown to have a distinctive prediction of ovarian reserve. A cumulative score of >14 was shown to be more accurate in predicting low ovarian reserve than age, day 3 FSH, or antral follicle count separately. Moreover, a score of >14 was shown to have a sensitivity of 88% and a specificity of 69% in predicting low ovarian reserve. More important, women with a score of >14 had significantly lower clinical implantation and pregnancy rates relative to women with a score of Conclusion(s): A novel and simple multivariate score using clinical and basal endocrine and sonographic parameters has a distinctive prediction of low ovarian reserve in infertile women undergoing assisted reproductive technology treatment. Moreover, it has the potential to predict clinical implantation and pregnancy rates in women with low and good ovarian reserve. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether seminatural cycle is a reasonable management for ovarian aging patients. Design: Prospective study. Setting: ART Unit, Clamart, France. Patient(s): Seventy-five women, 158 cycles. Intervention(s): Infertile women who presented with ovarian aging (defined as low ovarian reserve and characterized by cycle day 3 high FSH, high E2, and/or low inhibin B and/or previous cycle cancellations due to poor ovarian response to COH) were studied. Patients were offered up to three cycles. Treatment was scheduled as follows. From cycle day 8 onward the selection of the dominant follicle was monitored by ultrasound and hormonal measurements. When the dominant follicle appeared, patients received GnRH antagonist and, thereafter, hMG to support further follicular development. Main Outcome Measure(s): Implantation rate and clinical pregnancy. Result(s): Twenty-eight of 158 cycles were cancelled (17.7%). Oocyte pickups were performed in 119 (75.3%) cycles, 91 (57.6%) mature oocytes were retrieved, and 67 (42.4%) embryos transferred. Nineteen clinical pregnancies were obtained; the cumulative pregnancy rate per patient, after 3 cycles, was 35.2%. Conclusion(s): Use of a seminatural cycle is a reasonable management for patients with ovarian aging who have ovulatory menstrual cycles. It achieves a high implantation rate (28.3%). [Copyright &y& Elsevier]

Objective: To assess whether hyperbaric oxygen sessions elevate serum levels of anti-Müllerian hormone (AMH) in patients diagnosed with infertility with serum levels of less than or equal to 1 ng/dl AMH., Methods: A study was performed on 4 patients diagnosed with infertility. Serum AMH level was measured at the beginning and end of hyperbaric oxygen sessions, and endometrial thickness was measured on endometrial cycle day 14 before and during the hyperbaric oxygen sessions., Results: In two of the four patients, the serum AMH level increased by 40% and 116%. In one patient the serum AMH level was not elevated, with a serum AMH level before and after treatment of 0.1 ng/dl. The fourth patient became pregnant during the hyperbaric oxygen sessions. Endometrial thickness was not improved in any of our patients., Conclusions: This study showed that hyperbaric oxygen sessions can increase serum AMH levels, with a significant increase of 116% in one case. Therefore, this therapy can be used as an alternative treatment for patients with serum AMH levels of less than or equal to 1 ng/dl and a limited number of eggs for IVF cycles but not for patients with serum AMH levels of less than or equal to 0.1 ng/dl, as we did not observe an increase in serum AMH level in patients with an initial AMH level of 0.1 ng/dl. This study did not demonstrate improvement in endometrial growth following hyperbaric oxygen sessions.

Objective: To describe the first reported case of a seizure in a patient using the dietary supplement DHEA in an attempt to improve ovarian oocyte production. Design: Case report. Setting: University-affiliated teaching hospital, neurologic department. Patient(s): A 30-year-old woman with fragile X syndrome and no history of any convulsive disorder who was receiving IVF treatment. Intervention(s): Daily treatment with the dietary supplement DHEA. Main Outcome Measure(s): Generalized seizure. Result(s): After 1 month of DHEA treatment, the patient was admitted with a generalized seizure. Conclusion(s): A generalized seizure, associated with concurrent intake of DHEA. [Copyright &y& Elsevier]

Objective: To determine whether or not the level of serum anti-Müllerian hormone (AMH) is related to early ovarian aging in young women (< 35 years of age) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles., Design: Retrospective cohort study., Setting: An IVF laboratory in a university hospital in Taiwan. Patient (s): 70 young women (< 35 years of age) with low level of serum AMH (< 2 ng/ml) and 104 young women with level of serum AMH (≥ 2 ng/ml) who underwent IVF/ICSI cycles between January 2011 and November 2012 were enrolled. Intervention (s): None. Main outcome measure (s): Number of oocytes, fertilization rate, embryo quality, cycle cancellation rate, clinical pregnancy/abortion rate, and perinatal/infant outcomes., Results: The clinical pregnancy rate per transfer was favorable (low AMH group vs. normal AMH group [47.2% and 47.9%]) for women < 35 years of age, including women with a low serum AMH. Similarly, the live birth rate per transfer (low AMH group vs. normal AMH group [37.7% and 35.4%]) and perinatal outcomes were also comparable between the two groups. A significantly higher cycle cancellation was noted in the low AMH group than the normal AMH group (24.2% vs. 7.6%)., Conclusion: Although early ovarian aging should be taken into consideration for young and infertile women with low AMH level than expected, our results suggest that low serum AMH level may suggest early ovarian aging in accelerated oocyte loss only, but may not fully represent "early ovarian aging" based on the favorable outcomes of pregnancy.