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Dehydroepiandrosterone (DHEA) is frequently integrated as an adjuvant in over a quarter of controlled ovarian hyperstimulation (COH) protocols, despite the ongoing debate regarding its impact. This study aimed to evaluate the efficacy and mechanism of action of DHEA on ovarian follicular development and ovarian response in rats with varying ovarian reserves. The study involved 75 rats categorized into 15 distinct groups. The ovarian tissues of rats in both the normal ovarian reserve group and the premature ovarian insufficiency (POI) group, induced by 4-vinylcyclohexene diepoxide (VCD) injection, were subjected to histomorphological and biochemical analyses following the administration of DHEA, either alone or in combination with COH. Follicle counting was performed on histological sections obtained from various tissues. Serum concentrations of anti-Müllerian hormone (AMH) and the quantification of specific proteins in ovarian tissue, including phosphatase and tensin homolog of chromosome 10 (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT), cyclooxygenase 2 (COX-2), caspase-3, as well as assessments of total antioxidant status and total oxidant status, were conducted employing the ELISA method. The impact of DHEA exhibited variability based on ovarian reserve. In the POI model, DHEA augmented follicular development and ovarian response to the COH protocol by upregulating the PTEN/PI3K/AKT signaling pathway, mitigating apoptosis, inflammation, and oxidative stress, contrary to its effects in the normal ovarian reserve group. In conclusion, it has been determined that DHEA may exert beneficial effects on ovarian stimulation response by enhancing the initiation of primordial follicles and supporting antral follicle populations.

Background: An unexpected impaired ovarian response pertains to an insufficient reaction to controlled ovarian hyperstimulation. This deficient reaction is identified by a reduced count of mature follicles and retrieved oocytes during an IVF cycle, potentially diminishing the likelihood of a successful pregnancy. This research seeks to examine whether the characteristics of antral follicles can serve as predictive indicators for the unexpected impaired ovarian response to controlled ovarian stimulation (COS)., Methods: This retrospective cohort study was conducted at a tertiary university hospital. The electronic database of the ART (assisted reproductive technologies) center was screened between the years 2012-2022. Infertile women under 35 years, with normal ovarian reserve [anti-Müllerian hormone (AMH) > 1.2 ng/ml, antral follicle count (AFC) > 5] who underwent their first controlled ovarian stimulation (COS) cycle were selected. Women with < 9 oocytes retrieved (group 1 of the Poseidon classification) constituted the group A, whereas those with ≥ 9 oocytes severed as control (normo-responders) one (group B). Demographic, anthropometric and hormonal variables together with COS parameters of the two groups were compared., Results: The number of patients with < 9 oocytes (group A) was 404, and those with ≥ 9 oocytes were 602 (group B). The mean age of the group A was significantly higher (30.1 + 2.9 vs. 29.4 + 2.9, p = 0.01). Group A displayed lower AMH and AFC [with interquartile ranges (IQR); AMH 1.6 ng/ml (1-2.6) vs. 3.5 ng/ml (2.2-5.4) p < 0.01, AFC 8 (6-12) vs. 12 (9-17), p < 0.01]. The number of small antral follicles (2-5 mm) of the group A was significantly lower [6 (4-8) vs. 8 (6-12) p < 0.01), while the larger follicles (5-10 mm) remained similar [3 (1-5) vs. 3(1-6) p = 0.3] between the groups., Conclusion: The propensity of low ovarian reserve and higher age are the main risk factors for the impaired ovarian response. The proportion of the small antral follicles may be a predictive factor for ovarian response to prevent unexpected poor results., (© 2023. The Author(s).)

This study investigates the triple combination of adjuvants (low molecular weight heparin (LMWH)-aspirin-prednisolone) whether it improves the live birth rates of IVF&ICSI patients with previous implantation failure. This retrospective study included 1095 patients with >2 failed either fresh or frozen single embryo transfer cycles between 2014 Jan and 2021 Jan. Patients were divided into two subgroups. Group A consisted of patients with only vaginal progesterone for luteal phase support. Group B consisted of patients with triple (daily subcutaneous LMWH, daily 150 mg aspirin, and daily 16 mg prednisolone) luteal phase supplementation to vaginal progesterone. Demographic parameters, cycle characteristics, embryology, and pregnancy outcomes were compared, and the study's primary outcome was the live birth rate. Demographic parameters were similar between the groups. Positive b-hCG, miscarriage, and live birth rates were similar between groups as Group A vs. Group B, positive b-hCG 30.8% (190/617) vs. 35.4% (169/478), miscarriage rates 4.4% (27/617) vs. 6.7% (32/478), and live birth rates 20.4% (126/617) vs. 23.8% (114/478), respectively. When patients were stratified according to previous failures, live birth rates were still similar. Pregnancy outcomes were significantly improved in only patients with diminished ovarian reserve (Group A vs. Group B, positive b-hCG 24.2% vs. 34.3%, live birth rate 12.1% vs. 21.9%, p < 0.01). Whether the embryo transfer was fresh or frozen-thawed did not affect the results. A combined supplementation of LMWH, aspirin, and prednisolone in the luteal phase does not improve live birth rates of IVF&ICSI patients with previous implantation failure except potentially for patients with diminished ovarian reserve., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

This retrospective study aims to determine the more predictive ovarian reserve marker when there is discordance between anti-Müllerian hormone (AMH) and antral follicle count (AFC) in patients with diminished ovarian reserve (DOR). Patients who underwent ICSI because of DOR were divided into three groups. Group 1: patients with low AMH (<1.1 ng/ml) and AFC ( n  < 7), group 2: patients with low AMH (<1.1 ng/ml) and normal AFC ( n  ≥ 7) and group 3: patients with normal AMH (≥1.1 ng/dl) and low AFC ( n  < 7). Demographic values, follicle output rate (FORT) score and follicle to oocyte index (FOI) score of the groups were compared. Totally, 662 cycles were enrolled in the study. There were 418 cycles in group 1, 167 cycles in group 2 and 77 cycles in group 3. As the primary result, FORT and FOI scores were higher in group 3 than the other two groups. Median FORT Score with quartiles: group 1: 100 (66-150), group 2: 71 (57-100), group 3: 136 (96-200), p <.01 - median FOI score with quartiles: group 1: 83 (50-140), group 2: 71 (40-100), group 3: 116 (66-216), p <.01. In conclusion, serum AMH level has more predictive value for stimulation success if there is discordance with AFC.Impact Statement What is already known on this subject? Female age, serum Anti-Müllerian Hormone (AMH) levels, and antral follicle count (AFC) are commonly used to assess ovarian reserve and predict response to ovarian stimulation. AMH and AFC are both positively correlated with ovarian reserve. What do the results of this study add? If there is discordance between AFC and AMH in patients with diminished ovarian reserve (DOR), the ovarian response is better in patients with high AMH and low AFC than the patients with low AMH and high AFC. What are the implications of these findings for clinical practice and/or further research? It is important to assess both AFC and AMH before controlled ovarian hyperstimulation, to predict ovarian response in DOR patients, rather than assessing AFC or AMH alone.

The objective of this study was to assess the effect of rescue in vitro maturation and immediate intracytoplasmic sperm injection (ICSI) application on fertilisation success and early embryonic development of metaphase I (MI) oocytes. This was a retrospective cohort study including 2425 sibling oocytes in 259 ICSI cycles. ICSI was performed on 104 GV (germinal vesicle) oocytes which had reached the metaphase II (MII) stage (Group 1) and 231 MI oocytes which had reached the MII stage (Group 2) following IVM (in vitro maturation). Immediate ICSI was applied following oocyte aspiration on 292 MI stage (Group 3) and 1798 MII stage oocytes (Group 4). Normal fertilisation rates in Groups 1, 2, 3 and 4 were 51.9%, 39%, 30.1% and 59.5%, respectively. The rates of blastocyst development per oocyte and per zygote were calculated as 3.8%, 3.0%, 6.8%, 14.1% and 7.4%, 7.7%, 22.7%, 23.6% for Groups 1, 2, 3 and 4, respectively. The blastocyst development rate was significantly higher in the MI-ICSI group compared with other immature oocytes. Even though performing ICSI on the oocytes at the MI stage on the day of oocyte aspiration resulted in lower fertilisation rates, it was associated with significantly higher rates of blastocyst development.

Objective: To determine the predictive value of cryopreserved embryos during single fresh blastocyst transfer., Methods: This retrospective cohort study was conducted at a tertiary university hospital ART center. Patients who underwent a single fresh blastocyst transfer were selected from the electronic database. Patients with diminished ovarian reserve, uterine pathology, advanced age (>40 years) were excluded from the study. Patients were divided into two groups. Group A consisted of patients with only one available embryo for the fresh transfer. Group B consisted of patients with cryopreserved embryos apart from the fresh transferred embryo. Demographic and embryology parameters, pregnancy results were compared., Results: Demographic values, ovarian reserve parameters were comparable between groups. The number of the picked-up oocyte, metaphase-2 oocyte, and two-pronucleus embryo was lower in Group A. Positive pregnancy rates were two-fold higher in Group B (23.4% vs. 50.9% p  < .01). Pregnancy results did not change depending on the number of cryopreserved embryos in Group B., Conclusion: According to our results, the presence of cryopreserved embryos results in higher pregnancy rates in patients with fresh blastocyst embryo transfer independent from the woman's age and ovarian reserve. Thus, these results may help us to predict the implantation rate before embryo transfer.

In this retrospective multicenter cohort study, women with congenital hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic sperm injection in-between 2010-2014 were compared to age-matched controls with tubal factor infertility (n = 114) to assess ovarian stimulation cycle and pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6% in CHH and controls groups, respectively (p = 0.36). Comparable success rates were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78-2.67, p = 0.24). Of the 57 women with CHH, 19 were stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH-agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25 cases. Compared to women with PS, women without PS had significantly higher embryo implantation rates (21.6 versus 52.6%, p = 0.03). Although there was a trend favoring no PS, LBRs (25.0 versus 40.0%, p = 0.26) per cycle were short of statistical significance. LBRs per cycle (57.1 versus 31.2%, p = 0.11) and miscarriage rates (11.1 versus 16.7%, p = 0.75) were similar between CHH women who were given estrogen + progesterone and progesterone alone to support the luteal phase. In conclusion, the optimal stimulation protocol appears to be exogenous gonadotropin stimulation alone, without PS, and progesterone-only luteal phase support in CHH patients.

Study Questi̇on: Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma?, Summary Answer: Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma., What Is Already Known: Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas., Study Design, Size, Duration: A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period., Participants/materials, Setting, Methods: Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded., Main Results and the Role of Chance: Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3)., Limitations, Reasons for Caution: The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment., Wider Implications of the Findings: The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified., Study Funding/competing Interest(s): No funding or competing interests to declare., Trial Registration Number: None., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

This hypothesis generating study investigated whether GnRH antagonist cycles can be scheduled by a short course of oral estradiol administration during the follicular phase without impairing treatment outcome. Thirty-five women who underwent follicular phase estrogen scheduling (ES) of GnRH antagonist cycles were retrospectively matched for age and number of prior failed cycles with 35 women who underwent unscheduled GnRH antagonist cycles. ES group was given 6 mg/day estradiol orally from cycle day 2 until (including) one day before the scheduled start of stimulation. Gonadotropins were started on cycle days 2-3 in the control group. Flexible GnRH antagonist protocol was employed in both groups. ES group received estradiol for a median of 5 days. Total gonadotropin consumption was similar but one more GnRH antagonist injection was required in the ES group. Endometrial thickness on the day of hCG injection was increased in the ES group (12 versus 10 mm, p < 0.01). Number of oocytes, metaphase II oocytes and transferred embryos were similar. Embryo implantation rates were 44.8% versus 34.4% (p = 0.3), and clinical pregnancy rates were 48.6% versus 37.1%, (p = 0.33) in the ES and control groups, respectively. All women in the ES group had oocyte retrieval and embryo transfer within the desired period.

Objectives: The protective effect of CDP-choline in spinal cord transection and the mediation of its cardiovascular effects were investigated., Methods: Spinal cords of rats were transected at the T1-T2 levels. CDP-choline (250 mg/kg; intravenous) was administered 2 h and/or 24 h after the injury., Key Findings: Spinal cord transection caused severe tissue damage, decreased mean arterial pressure, heart rate, plasma adrenaline, and noradrenaline but increased plasma vasopressin levels. Repeated CDP-choline treatment attenuated the degree of tissue injury. Administration of CDP-choline at 2 h after transection transiently increased blood pressure and decreased heart rate, while it produced a small decrease in blood pressure and heart rate when it was given at 24 h. Plasma adrenaline levels were higher in the group where CDP-choline was given repeatedly. Plasma noradrenaline and vasopressin levels did not change additionally after CDP-choline injections in all groups. In order to determine if CDP-choline attenuates the oxidative injury induced by transection, we measured blood superoxide dismutase, glutathione peroxidase activity and malondialdehyde levels. Repeated CDP-choline administration decreased blood superoxide dismutase and glutathione peroxidase activity without any effect on malondialdehyde levels., Conclusions: Data indicate that repeated intravenous CDP-choline treatment prevents tissue damage in spinal shock conditions in the acute phase. The cardiovascular effects of the drug do not seem to be responsible for this protection but the drug-induced attenuation of the oxidative stress may play a role.

Purpose: To evaluate quantitatively the apoptotic activity after intravitreal injections of pegaptanib sodium and bevacizumab in the rabbit retina., Methods: Different doses of bevacizumab (0.25, 0.625, 1.25, and 2.5 mg) and pegaptanib sodium (0.15, 0.3, and 0.6 mg) were injected intravitreally in 48 rabbits. The eyes were enucleated at different times for early studies at day 14 and for late studies at 3 months after a single injection or at 3 months, with 1 injection in each of the 3 months (day 90). The time course and dose-response of photoreceptor cells in the rabbit retina after intravitreal injection of bevacizumab or pegaptanib sodium were examined by histologic analysis with hematoxylin and eosin (H&E) staining, caspase-3 and -9 immunostaining, and in situ terminal-deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments of paraffin-embedded sections., Results: No sign of retinal toxicity was seen in H&E stained histologic sections of eyes that had received bevacizumab or pegaptanib sodium. Nuclear DNA fragmentation in the outer retinal layers shown by the TUNEL method was evident in the high-dose groups (55.3% with 1.25 mg and 64.5% with 2.5 mg bevacizumab, and 48.5% with 0.6 mg pegaptanib sodium) at 14 days and also in the clinical dose groups (49.8% with three injections [1 each month] of 0.625 mg bevacizumab and 44.3% with 0.15 mg pegaptanib sodium) at 90 days. The ratios of TUNEL-positive cells in physiologic saline and the sham-control groups were 32.3% and 21%, respectively., Conclusions: Intravitreal injection of bevacizumab and pegaptanib sodium caused a significant increase in apoptotic activity in rabbit photoreceptor cells. However, although bevacizumab caused increasing apoptotic activity at higher doses, similar dose-dependent adverse effects were not evident for pegaptanib sodium.

Purpose: To evaluate the preclinical safety of intravitreal bevacizumab, which is a full-length humanized monoclonal antibody against the vascular endothelial growth factor (VEGF), in rabbit eyes over a short-term period., Methods: Twenty-four rabbits were divided into two groups, each with two subgroups. The first group (groups 1 and 2) received 1.25 mg (0.05 mL) intravitreal bevacizumab, and the second group (groups 3 and 4) received 3.00 mg (0.12 mL) intravitreal bevacizumab. The right eyes were designated as the study eyes, and the left eyes served as a control and received the same volume of saline intravitreally. Groups 1 and 3 were labeled as early groups and scheduled to be terminated at 14 days. Groups 2 and 4, labeled as late groups, were scheduled to be terminated at 28 days. Besides electroretinography (ERG) and visually evoked potentials (VEP), central corneal thickness, intraocular pressure, fundus photography, and anterior segment imaging were performed at baseline and scheduled time points. Enucleated eyes were preserved for light and electron microscopic investigation., Results: No anterior segment inflammation was observed, except in one eye in group 1 which showed a uveitic reaction. No evidence of retinal toxicity was seen with intravitreal bevacizumab at doses of 1.25 and 3.00 mg, by either ERG or light microscopy. Electron microscopic assessment revealed mitochondrial damage in the inner segments of photoreceptors. Immunohistochemical staining with bax and caspase-3 and -9 showed intensive apoptotic protein expression in all study sections and minimal expression in the control eyes., Conclusions: Although electrophysiologic investigation and light microscopy showed normal retinal function and structure, mitochondrial disruption in the inner segments of photoreceptors was detected by electron microscopy, and apoptotic expression was detected after the injection of intravitreal bevacizumab.

Purpose: To evaluate the efficacy of newly developed antifungal agents caspofungin and voriconazole in Candida albicans endophthalmitis in rabbit eyes., Methods: Thirty New Zealand white rabbits were divided into four treatment groups and one control group. One eye of each rabbit was infected by inoculation of 1 x 10(4) CFU/ml of C. albicans. Seventy-two hours after the inoculation, caspofungin 100 microg/0.1 ml in group 1 (n = 6), voriconazole 50 microg/0.1 ml in group 2 (n = 6), amphotericin B 10 microg/0.1 ml in group 3 (n = 6), itraconazole 10 microg/0.1 ml in group 4 (n = 6), and 0.1 ml NaCl 0.9% in control group (n = 6) were injected into the vitreous cavity. Clinical and histopathologic examination scores and microbiological analysis of vitreous aspirates were compared., Results: There was statistically significant difference in the clinical scores, histopathologic scores, and mean CFU/ml between the treatment and control groups (p < 0.05). In caspofungin and voriconazole groups, histopathologic scores and mean CFU were lower than other treatment groups and control group., Conclusions: Intravitreal injection of caspofungin and voriconazole was effective against C. albicans endophthalmitis in this experimental rabbit model.

Purpose: In this study we evaluated the efficiency of diluted triamcinolone particles in peeling of the internal limiting membrane (ILM) in cases of diffuse diabetic macular oedema., Methods: A prospective observational study of thirteen consecutive patients with diffuse diabetic macular oedema who had undergone ILM peeling aided by use of a diluted (1 mg mL(-1)) suspension of triamcinolone particles (0.05 mg). The results were assessed by measurement of visual acuity and intraocular pressure, by ophthalmoscopy, and by fluorescein angiography., Results: ILM peeling in all eyes could be performed easily and completely with the aid of triamcinolone particles homogeneously dispersed over the macular ILM. During the peeling procedure, triamcinolone particles resulted in clear contrast between the peeled and unpeeled ILM thus enabling us to easily find the edge of the ILM and to be able to continue peeling at further attempts. In twelve of the thirteen eyes the macular oedema was completely resolved or reduced. Visual acuity improved by at least two lines in nine eyes (70%). The intraocular pressure increase did not exceed 21 mmHg in any of the patients., Conclusions: The diluted triamcinolone suspension enables good visualisation of the ILM during the ILM peeling procedure in cases of diffuse diabetic macular oedema. Use of a diluted suspension may reduce the risk of intraocular pressure increase and the potential toxicity of triamcinolone.

Background: To evaluate the results of pars plana vitrectomy with peeling of the internal limiting membrane (ILM) in eyes with chronic macular oedema., Methods: PPV with indocyanine green (ICG) assisted peeling of the ILM was performed in 33 eyes with diabetic (21 eyes) or non-diabetic (12 eyes) macular oedema. Postoperatively, resolution of macular oedema, improvement of visual acuity (VA) and complications were documented. The peeled membranes were submitted for light and transmission electron microscopic evaluation., Results: The mean follow-up time was 12.2 months. The macular oedema decreased or was resolved in 17 (81%) eyes in the diabetic group and in 11 (92%) eyes in the non-diabetic group. VA improved by at least 2 lines in 11 (52%) eyes in the diabetic group and in 7 (58%) eyes in the non-diabetic group. The difference between visual acuity improvements of the two groups was not statistically significant (P>0.05). However, in the diabetic group the difference of visual improvement between cystoid and diffuse type of macular oedema eyes was statistically significant (14% versus 71%, P=0.02). Light and transmission electron microscopy showed the presence of ILM in all specimens. During the follow-up period no recurrence of macular oedema or epiretinal membrane formation was observed., Conclusion: Pars plana vitrectomy with peeling of the ILM and epiretinal membrane leads to the resolution of macular oedema in the majority of eyes. This however, is not always associated with VA improvement. In diabetic eyes, cystoid type of macular oedema appears to be a poor prognostic factor for improved VA.

Background and Objective: The efficiency of indocyanine green (ICG) dye in the removal of the internal limiting membrane (ILM) with a fluid needle using passive aspiration was evaluated., Patients and Methods: Eighteen consecutive patients with diffuse diabetic macular edema were studied. After vitrectomy and total fluid-air exchange, 0.1 mL of ICG solution 0.25% was left in the macular area for 1 minute. Then the macular ILM was peeled with a specially designed tapered fluid needle using passive aspiration., Results: In 16 of the 18 eyes, the peeling procedure could be easily performed with a tapered fluid needle using passive aspiration. In 11 eyes, partial development of spontaneous ILM detachment prior to the peeling process was also observed., Conclusions: ICG solution 0.25% appears to reduce the adhesive force of the ILM to the sensory retina, which makes the removal of the ILM much easier by passive aspiration with a fluid needle.