Luteinizing hormone supplementation in controlled ovarian stimulation: the Iran Delphi consensus.

Introduction: Numerous consensus documents worldwide address luteinizing hormone (LH) supplementation in controlled ovarian stimulation, yet to the best of our knowledge, only one consensus paper has been published in the Arab region. This study presents a Delphi consensus by seven Iranian infertility experts, offering real-world clinical perspectives. The aim was to develop evidence-based opinions on LH's role alongside FSH in various aspects of assisted reproductive technology (ART), including LH levels, monitoring, r-hLH use, and suggested activity. Methods: Employing the Delphi consensus approach, the Iran consensus unfolded in three steps. In Step 1, eight out of 10 statements gained approval, while two unclear statements were removed. In Step 2, the 20-member extended panel voted on the remaining eight statements. Results: Only one (statement 3) lacked consensus (55% agreement), prompting a modification. The revised statement (noted as statement 3') obtained an 83% agreement. Discussion: The clinical perspectives included in this consensus complement clinical guidelines and policies that help further improve treatment outcomes, especially for patients with FSH and LH deficiencies.

Prevalence of chronic endometritis in infertile women undergoing hysteroscopy and its association with intrauterine abnormalities: A Cross-Sectional study.

OBJECTIVE: Chronic endometritis (CE) is an inflammatory condition with several different risk factors. We aimed to examine whether intrauterine abnormalities, such as endometrial polyps, submucosal myomas, intrauterine adhesions, or a septate uterus, were associated with an increased likelihood of developing chronic endometritis. METHODS: A cross-sectional study was conducted on 335 infertile women who underwent hysteroscopy surgery at the Ayatollah Taleghani Hospital Infertility Center, affiliated by Shahid Beheshti University of Medical Sciences, in 2022. All participants in the study underwent hysteroscopic surgery, which allowed for direct visualization of the intrauterine cavity, and endometrial biopsies were taken for further analysis. To characterize endometritis, plasma cell infiltration was assessed. Patients with ≥5 plasma cells observed in 10 high-power fields were defined as having chronic endometritis. RESULTS: Endometritis was observed in 51.3% of the patients, totaling 172 individuals. Logistic regression analysis revealed that patients with endometrial polyps had 5.2 times higher odds of developing endometritis compared to patients without polyps (95% CI = 2.9, 9.2) (p-value <0.001). Similarly, patients with intrauterine adhesions had a significant increase in the odds of endometritis (OR = 4.6, 95% CI = 2.1, 10.1) (p-value <0.001). CONCLUSIONS: Treatment or removal of endometrial abnormalities through hysteroscopic procedures may help to reduce the risk of chronic endometritis and improve fertility outcomes. Further research is necessary.

D-chiro-inositol in clinical practice: A perspective from The Experts Group on Inositol in Basic and Clinical Research (EGOI).

BACKGROUND: D-chiro-inositol is a natural molecule that, in association with its well-studied isomer myo-inositol, may play a role in treating various metabolic and gynecological disorders. OBJECTIVES: This perspective seeks to explore the mechanisms and functions of D-chiro-inositol, laying the foundations to discuss its use in clinical practice, across dysmetabolism, obesity, and hormonal dysregulation. METHODS: A narrative review of all the relevant papers known to the authors was conducted. OUTCOME: D-chiro-inositol acts through a variety of mechanisms, acting as an insulin sensitizer, inhibiting the transcription of aromatase, in addition to modulating white adipose tissue/brown adipose tissue trans differentiation. These different modes of action have potential applications in a variety of therapeutic fields including: PCOS, dysmetabolism, obesity, hypoestrogenic/hyperandrogenic disorders, and bone health. CONCLUSIONS: D-chiro-inositol mode of action has been studied in detail in recent years, resulting in a clear differentiation between D-chiro-inositol and its isomer myo-inositol. The insulin sensitizing activities of D-chiro-inositol are well understood; however, its potential applications in other fields, in particular obesity and hyperestrogenic/hypoandrogenic disorders in men and women, represent promising avenues of research that require further clinical study.

Comparing the effect of sequential embryo transfer versus double blastocyst embryo transfer on pregnancy outcomes in intracytoplasmic sperm injection (ICSI) cycles in patients with repeated implantation failure: A randomized controlled trial.

OBJECTIVE: Recurrent implantation failure (RIF) is the main challenge in assisted reproductive technology (ART) practice. Sequential embryo transfer, in which both, cleavage-stage embryo on day 3 and blastocyst on day 5, are sequentially transferred in the same cycle, has been suggested for increasing embryo implantation in RIF patients. The aim of the present study was to compare the effect of sequential embryo transfer versus double blastocyst embryo transfer on pregnancy outcomes in intracytoplasmic sperm injection (ICSI)/frozen embryo transfer (FET) cycles in RIF patients. MATERIALS AND METHODS: This prospective study was enrolled 224 RIF patients undergoing ICSI/FET cycles and randomly divided to sequential and control groups. In sequential group, embryo transfer was conducted on day 3 (cleavage stage) and day 5 (blastocyst stage). In control group, two top-quality blastocysts were transferred on day 5. RESULTS: Two hundred and two couples accomplished the trial, and their data were analyzed. Results demonstrated that sequential embryo transfer on day 3 and day 5 compared to double blastocyst transfer on day 5 significantly increased implantation rate, clinical pregnancy rate and ongoing pregnancy rate in RIF patients (p-value = 0.0142, p-value = 0.0154, p-value = 0.0201, respectively). However, there were no significant differences in terms of chemical pregnancy rate, multiple pregnancy rate, miscarriage rate and ectopic pregnancy rate in the studied groups. CONCLUSION: Sequential embryo transfer is associated with improved pregnancy outcomes in RIF patients. Further prospective studies with larger sample sizes are required to validate these results.

Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger and freeze-all strategy in GnRH antagonist protocol; case report and literature review.

Ovarian hyperstimulation syndrome (OHSS) is characterized by increased vascular permeability, hemoconcentration and fluid leakage to the third space. The vast majority of OHSS cases occur following ovarian stimulation for IVF. This potentially lethal iatrogenic condition is one of the most serious complications of assisted reproductive technologies. We report one case of severe early OHSS after GnRH agonist trigger in a GnRH antagonist protocol and freeze-all approach without the administration of any hCG for luteal-phase support in a 34-year-old case of PCO with 7 years primary infertility. After oocyte retrieval the patient was seen at the emergency unit of the hospital with abdominal distension, pain, anuria, dyspnea, and OHSS symptoms. The diagnosis was OHSS with severe ascitis. She was admitted to the Intensive care unit (ICU). She was managed with oxygen by mask, intravenous fluids, anticoagulant and albumen, we performed a two-time vaginal ascites puncture, resulting in the removal of 7800mL of clear fluid in Intensive Care Unit with full recovery. This case study presents the clinical manifestations, investigation, progress, management, outcome and preventive measures. The patient was managed with no complications. Clinicians have to be aware that even the sequential approach to ovarian stimulation with a freeze-all approach and GNRH analog triggering does not completely eliminate OHSS in all patients.

The expression level of mir-21-3p in platelet-rich plasma: A potential effective factor and predictive biomarker in recurrent implantation failure.

Recurrent implantation failure (RIF) is the most important complication associated with in vitro fertilization (IVF). Despite the good quality of the transferred embryo, the success rate is rather disappointing. Therefore, predictive biomarkers for implantation are critical to making decisions about transferring high-quality embryos or cryopreserving them for cycles with a higher chance of implantation. Recently, intrauterine infusion of autologous platelet-rich plasma (PRP) has been proposed to increase the endometrial receptivity in RIF patients. PRP is rich in both growth factors and microRNAs (miRNAs). We investigated the possible association of mir-21-3p, mir-21-5p, mir-494-3p, mir-145-5p, and insulin-like growth factor-I (IGF-I) levels in PRP and platelet-poor plasma (PPP) samples with the pregnancy outcomes in RIF patients. The miRNA expression level and IGF-I concentration were assessed using real-time PCR and chemiluminescence methods respectively. Mir-21-3p was upregulated in PRP samples of the pregnant group in comparison to the nonpregnant group. There was no difference in the expression of mir-21-3p in PPP samples of these groups. The concentration of IGF-I was higher in PRP and PPP samples of the nonpregnant in comparison to the pregnant group. Receiver-operating characteristic curve analysis showed that mir-21-3p can be a valuable biomarker for the prediction of pregnancy chance in RIF patients treated with PRP.

Effect of autologous platelet-rich plasma for treatment of recurrent pregnancy loss: a randomized controlled trial.

OBJECTIVE: Recurrent pregnancy loss (RPL) is a fertility problem for which no exact mechanism of abortion or efficient treatment has been described. This study was conducted between 2018 and 2019 to investigate the effectiveness of autologous platelet-rich plasma (PRP) in improving the live birth rate of women with RPL who required in vitro fertilization (IVF). METHODS: A total of 63 patients with at least two previous pregnancy losses and no specific cause detected for the RPL were included and randomly assigned into two groups (PRP and control). Intrauterine infusion of 0.5 mL of autologous PRP was performed 48 hours before embryo transfer in the PRP group. Women in the control group received standard treatment. RESULTS: Forty patients completed the study. The baseline and cycle characteristics of the participants did not differ significantly between the PRP and control groups. The clinical pregnancy rate was higher in the PRP group (35% vs. 20%, P=0.288). The live birth rate was 15% in the PRP group, but no live births were recorded in the control group (P=0.231). CONCLUSION: This is the first study to show that intrauterine infusion of PRP in patients with RPL who undergo IVF may increase the chance of live birth.

Impact of ejaculatory abstinence period and semen characteristic on the reproductive outcomes after intracytoplasmic sperm injection.

OBJECTIVE: The prognostic of semen characteristics in intracytoplasmic sperm injection (ICSI) outcomes is not clear. Also, there is no evidence-based recommendation for the abstinence period before ICSI. So, we aimed to assess the influence of the abstinence period and semen characteristics on ICSI outcomes. METHODS: A total of 1003 fresh ICSI cycles were divided into six groups; group 1 (1-day abstinence), group 2 (2 days abstinence), group 3 (3 days abstinence), group 4 (4 days abstinence), group 5 (5 days abstinence), and group 6 (6-10 days abstinence). RESULTS: We showed that semen volume (p=0.0001) and total sperm count (p=0.005) were increased in the groups with higher abstinence periods. Other semen parameters did not significantly associate with the abstinence period. The percentage of progressively motile sperm was associated with fertilization rate (p=0.007), and the sperm morphology was associated with cleavage-stage embryo rate (p=0.036). No influence of abstinence or semen parameters on rates of pregnancies was observed. CONCLUSIONS: The abstinence period before ICSI can influence the semen volume and total sperm count, and possibly fertilization. Although the sperm with the highest quality are selected for ICSI, the percentages of progressively motile and morphologically normal sperm in the ejaculated semen have a predictive value for fertilization and cleavage rates after ICSI, respectively.

The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial.

Repeated implantation failure (RIF) is a disorder in which good-quality embryos fail to implant in the endometrium following several in vitro fertilization (IVF) cycles. This study aimed to evaluate the efficiency and safety of intrauterine infusion of platelet-rich plasma (PRP) in improvement of pregnancy outcomes in RIF patients undergoing frozen embryo transfer (FET). A total of 438 women with a history of RIF undergoing FET were assessed for eligibility to enter the study. Patients were randomly assigned to the intervention (PRP) and control groups. The intervention group received an intrauterine infusion of 0.5 ml PRP 48 h before embryo transfer while the control group received standard treatment. The rates of chemical and clinical pregnancy were defined as the primary outcome values. All women were followed up until the study endpoints that included the number of neonates born and pregnancy-related complications. Three hundred and ninety-three participants accomplished the study and their data were analyzed. The chemical pregnancy, clinical pregnancy, and live birth rates were higher in the PRP group than control group (p value: <0.0001; p value: <0.0001; p value: <0.0001 respectively). However, there were no significant differences between the two groups in terms of multiple pregnancies and pregnancy complications except for spontaneous abortion. The spontaneous abortion rate was significantly higher in the control group compared to the PRP group (p value = 0.0262). These results suggest that intrauterine infusion of PRP is an effective and safe route to improve pregnancy outcomes in RIF patients undergoing FET.

Involvement of single nucleotide polymorphisms in ovarian poor response.

PURPOSE: Unpredictability in acquiring an adequate number of high-quality oocytes following ovarian stimulation is one of the major complications in controlled ovarian hyperstimulation (COH). Genetic predispositions of variations could alter the immunological profiles and consequently be implicated in the variability of ovarian response to the stimulation. DESIGN: Uncovering the influence of variations in AMHR2, LHCGR, MTHFR, PGR, and SERPINE1 genes with ovarian response to gonadotrophin stimulation in COH of infertile women. METHODS: Blood samples of the women with a good ovarian response (GOR) or with a poor ovarian response (POR) were collected. Genomic DNA was extracted, and gene variations were genotyped by TaqMan SNP Genotyping Assays using primer-probe sets or real-time PCR Kit. RESULTS: Except for PGR (rs10895068), allele distributions demonstrate that the majority of POR patients carried minor alleles of AMHR2 (rs2002555, G-allele), LHCGR (rs2293275, G-allele), MTHFR (rs1801131, C-allele, and rs1801133, T-allele), and SERPINE1 (rs1799889, 4G allele) genes compared to the GOR. Similarly, genotypes with a minor allele in AMHR2, LHCGR, MTHFR, and SERPINE1 genes had a higher prevalence among POR patients with the polymorphic genotypes. However, further genotype stratification indicated that the minor alleles of these genes are not associated with poor response. Multivariate logistic analysis of clinical-demographic factors and polymorphic genotypes demonstrated a correlation between FSH levels and polymorphic genotypes of SERPINE1 in poor response status. CONCLUSIONS: Despite a higher prevalence of AMHR2, LHCGR, MTHFR, and SERPINE1 variations in the patients with poor ovarian response, it seems that these variations are not associated with the ovarian response.

Conditioned medium derived from seminal extracellular vesicles-exposed endometrial stromal cells induces inflammatory cytokine secretion by macrophages.

OBJECTIVE: Seminal plasma (SP) contains large numbers of sub-cellular structures called extracellular vesicles (EV) which have been postulated to have immunological functions due to their bioactive contents including proteins and small non-coding RNAs. Although the response of endometrial cells to seminal EV (SEV) is recently being elucidated, the impact of these signaling vesicles on stroma-immune crosstalk is still unknown. Herein, we aimed to investigate the effect of conditioned medium (CM) derived from SEV-exposed endometrial stromal cells (eSC) on cytokine secretion by macrophages. STUDY DESIGN: SEV were isolated from SP samples of healthy donors and characterized by common methods needed for EV characterization, including size determination by dynamic light scattering (DLS), transmission electron microscopy (TEM), and western blot analysis of EV markers. Endometrial biopsies were obtained from healthy individuals and eSC were isolated and characterized. EV internalization assay was performed by labeling the SEV with PKH67 green fluorescent dye. Then, the eSC were exposed to SEV and the CM was collected. Finally, the CM from SEV-exposed eSC was added to the macrophage culture and the level of inflammatory (interleukin (IL)-1α and IL-6) and anti-inflammatory (IL-10) cytokines were measured in the culture supernatant of macrophages. RESULTS: The results demonstrated that the CM derived from SEV-exposed eSC induce IL-1α and IL-6 secretion by the macrophages, while the secretion of IL-10 was reduced. CONCLUSION: Our results support the idea that the stroma-immune interaction is affected by SEV. This effect may be a part of immunoregulatory function of SP inside upper female genital tract and have an obvious impact during peri-implantation period.

Culture strategy as a modulator of target assessments: Functionality of suspension versus hanging drop-derived choriocarcinoma spheroids as in vitro model of embryo implantation.

The choriocarcinoma spheroid model has been amply applied to study the underlying molecular mechanism of implantation. Reproducibility and functionality of spheroid tumor models were addressed precisely. To mimic embryo-endometrium crosstalk, no functional characteristics of spheroids have been provided based on culture strategies. In this study, choriocarcinoma spheroids were provided as suspension culture (SC) or hanging drop culture (HDC). Primary assessments were performed based on morphology, cellular density, and hormonal secretion. Spheroid-endometrial cross talk was assessed as coculture procedures. Further, alkaline phosphatase (ALP) activity and expression of genes involved in attachment, invasion, and inducing migration were quantified. We found HDC spheroids provided a homogenous-shaped aggregate with a high grade of viability, cellular integration, hormonal secretion, and the dominant role of WNTs expression in their microarchitecture. SC spheroids showed a higher level of ALP activity and the expression of integrated genes in modulating attachment, invasion, and migration abilities. Spheroid confrontation assays clearly clarified the superiority of SC spheroids to crosstalk with epithelial and stromal cells of endometrium in addition to motivating an ideal endometrial response. Conclusively, culture strategies by affecting various molecular signaling pathways should be chosen precisely according to specific target assessments. Specifically, SC assumed as an ideal model in spheroid-endometrial cross talk.

Aberrant expression of BAX, MEG3, and miR-214-3P genes in recurrent pregnancy loss.

AIMS: Recurrent pregnancy loss (RPL), with unknown causes, is one of the most common challenges facing pregnancy. Apoptotic signaling pathways are involved in the normal and abnormal pregnancy process. Despite the evidence pointing toward the aberrant expression of apoptotic and apoptotic-related genes in pregnancy complications, the involvement of these genes in RPL remains to be elucidated. This study aimed to investigate the expression levels of BAX, MEG3, and miR-214-3p (as a microRNA), and their associations in an Iranian population. MATERIALS AND METHODS: Following the extraction of RNA from blood samples of RPL patients and controls, quantitative expression levels of BAX, MEG3, and miR-214-3p genes were analyzed by real-time RT-PCR. RESULTS: The findings showed that the expression levels of BAX and miRNA-214-3p were significantly higher in the blood samples of RPL patients than in control samples. In contrast, the expression of MEG3 was significantly down-regulated in women RPL. Furthermore, altered expressions of MEG3 and miRNA-214-3p are associated with their target gene BAX, where the BAX expression is positively and negatively correlated with the expressions of has-miR-214-3P and MEG3, respectively. ROC curve evaluation demonstrated the highest specificity and diagnostic value for miR-214-3p expression in distinguishing RPL samples from the healthy controls. CONCLUSIONS: These data indicated that the aberrant expression of BAX, MEG3, miRNA-214-3p genes in RPL patients could provide new insights into the biological characteristics and related pathways of differentially expressed genes, which could help as potential diagnostic biomarkers and a better understanding of the molecular mechanisms of RPL.

Comparison of Subcutaneous and Vaginal Progesterone Used for Luteal Phase Support in Patients Undergoing Intracytoplasmic Sperm Injection Cycles.

OBJECTIVE: Luteal phase defect in patients undergoing assisted reproductive technology (ART) is a sign of uterine failure due to insufficient progesterone effects on the endometrium. This study aims to compare the success rate and side effects of subcutaneous progesterone and vaginal progesterone to support the luteal phase in ART cycles. METHODS: In this prospective randomized study, we used the traditional intracytoplasmic sperm injection (ICSI), and we transferred one or two 4-8 cell fetuses based on the patient's age on the third day of inoculation. We started with luteal phase support from the day of oocyte recovery and the patients randomly received either a daily dose of 25mg subcutaneous progesterone (Prolutex, IBSA Switzerland) or a 400mg dose of vaginal progesterone (Cyclogest, Actoverco, United Kingdom) every 12 hours. If blood BHCG pregnancy test was positive, support for the luteal phase continued until week 10 of gestation. The measured outcomes were the clinical, chemical and ongoing pregnancy rates as well as the rate of early abortion, patients' acceptance, tolerance and satisfaction. RESULTS: The results of the present study showed that there was no statistically significant difference between clinical, chemical and ongoing pregnancy rates - as well as the rate of early abortion, and patients' satisfaction when comparing the two treatment Groups. CONCLUSIONS: it seems that the subcutaneous form of progesterone can be used in patients who are not willing to use vaginal progesterone, with similar treatment results and patient satisfaction, when compared to vaginal progesterone.

Efficacy of daily GnRH agonist for luteal phase support following GnRH agonist triggered ICSI cycles versus conventional strategy: A Randomized controlled trial.

OBJECTIVE: The use of gonadotropin-releasing hormone agonist (GnRHa) as an alternative for human chronic gonadotropin (hCG) trigger has potential benefits, but the optimal luteal phase support (LPS) following GnRHa trigger remains to be elucidated. We aimed to investigate a new strategy (daily GnRH agonist for LPS following GnRH agonist trigger) as an alternative for the conventional approach to the patients undergoing intracytoplasmic sperm injection (ICSI). METHODS: In this randomized controlled trial study, 44 ICSI patients were randomly assigned into two groups: group 1, patients received standard strategy (hCG trigger [10000 IU] and progesterone bid [400 mg/BD] for LPS); group 2, patients received a dose of GnRHa (0.2 mg) for ovulation trigger and subcutaneous injection of GnRHa bid (0.2 mg) for LPS. RESULTS: The pregnancy, miscarriage, and live birth rates for the patients undergoing LPS following the GnRHa trigger were similar to those of patients undergoing the standard strategy. CONCLUSIONS: We showed that a daily subcutaneous injection of GnRHa for LPS following the GnRHa trigger can be successfully performed as an alternative to the standard strategy, with comparable pregnancy and live birth rates in ICSI patients.

Effect of antioxidant supplementation containing L-carnitine on semen parameters: a prospective interventional study.

OBJECTIVE: One of the remarkable causes of infertility in men is oxidative stress having a reducing effect on their reproductive function. In the present study, we investigated the efficacy of supplementation with antioxidants and L-Carnitine (contained in Androferti) on semen parameters. METHODS: We included 180 infertile male patients diagnosed with idiopathic oligoastenoteratozoospermia (OAT) in this study, and we analyzed the semen sample from 59 patients before and after oral antioxidant treatment, with the commercial name of Androferti (containing 1500 mg of L-Carnitine, 60 mg of vitamin C, 20 mg of coenzyme Q10, 10 mg of vitamin E, 10 mg of zinc, 200 µg of vitamin B9, 50 µg of selenium, 1 µg of vitamin B12). All of the patients received Androferti twice a day for 3 months. RESULTS: There were significant improvements in the sperm concentration (p=0.004) after the antioxidant supplementation. There was also a meaningfully improvement in sperm morphology (p=0.01) after treatment. However, sperm motility was not significantly altered after antioxidant treatment (p=0.2). CONCLUSIONS: Antioxidants supplementation containing 1500 mg L-carnitine can improve the semen quality in infertile men diagnosed with idiopathic OAT. However, further studies are required to determine the antioxidant effects on reproduction function.

Pyrvinium pamoate induces in-vitro suppression of IL-6 and IL-8 produced by human endometriotic stromal cells.

Endometriosis, a chronic inflammatory disease, is identified by the presence of endometrial tissue outside the uterus. The prevalence of this disease among reproductive-age women is almost 10-15%. High levels of IL-6 and IL-8 have been found in the peritoneal fluid (PF) of women with endometriosis and are involved in its pathogenesis. Isolated stromal cells from 12 ectopic and eutopic endometrial biopsies of women with ovarian endometrioma and also 12 endometrial biopsies of nonendometriotic controls were treated with 1.1 µM pyrvinium pamoate, a Wnt/ß-catenin signaling pathway inhibitor, for 72 hrs. Before treatment, mRNA gene expression and secretion of IL-6 and IL-8 were significantly higher in ectopic (EESCs) than eutopic (EuESCs) and control (CESCs) endometrial stromal cells. After treatment, mRNA gene expression and also secretion of IL-6 and IL-8 were significantly reduced. Our Findings showed that pyrvinium pamoate suppresses the mRNA gene expression and secretion of IL-6 and IL-8 in human endometriotic stromal cells. Additional investigations on this compound are required before clinical application.

Correction to: Does timing in ICSI cycle affect oocyte quality and reproductive outcomes? A prospective study.

In the original article published, the values given in the variables are incorrect.

Does timing in ICSI cycle affect oocyte quality and reproductive outcomes? A prospective study.

PURPOSE: To evaluate the association of time intervals between various steps of the intracytoplasmic sperm injection (ICSI) cycle with oocyte quality and reproductive outcomes. METHODS: We conducted a prospective study among patients undergoing ICSI cycles in an academic hospital between May 2017 and January 2019. The time intervals between the various steps of cycles were recorded. The ICSI cycles were categorized according to the different time intervals; human chorionic gonadotropin (hCG) injection to oocyte pick up (hCG-OPU) (≤ 36 h and > 36 h), OPU-denudation (≤ 2 h and > 2 h), and denudation-ICSI (≤ 2 h and > 2 h). The main outcome measures were oocyte dysmorphisms, fertilization, cleavage, biochemical, and clinical pregnancy rates. RESULTS: A total of 613 ICSI cycles using fresh autologous oocytes were included in this study. After adjusting for confounders, the hCG-OPU interval was associated with the presence of cytoplasmic granulation, inclusion body, and also the total number of morphologically abnormal premature oocytes in the cycle (P = 0.02, P = 0.04, P = 0.008, respectively). OPU-denudation interval was associated with cytoplasmic granulation and extended perivitelline space of the oocytes (P = 0.006 and P = 0.03, respectively). The denudation-ICSI interval was only associated with cytoplasmic granulation (P = 0.01). However, hCG-OPU, OPU-denudation, and denudation-ICSI intervals were not significantly associated with fertilization, cleavage, biochemical, and clinical pregnancy rates. CONCLUSIONS: All the studied time intervals between various steps of ICSI procedure could affect oocyte quality, but the oocyte dysmorphisms were mainly associated with hCG-OPU interval. However, the time intervals were not associated with fertilization, cleavage, and pregnancy outcomes.

Effect of myo-inositol supplementation on ICSI outcomes among poor ovarian responder patients: A randomized controlled trial.

PURPOSE: This study has evaluated the use of myo-inositol supplementation for improving reproductive outcomes in poor responders undergoing intracytoplasmic sperm injection (ICSI). METHODS: One hundred and twelve poor responder patients were included in the study and randomly categorized into two groups using a permuted block randomization method. Group A included 56 patients who received myo-inositol (4 g) and folic acid (400 µg) daily from one month before starting the ICSI cycle continuing until the ovulation triggering day. Group B included 56 patients consuming only folic acid (400 µg) daily for the same period. The outcome measures were the number of retrieved oocytes, embryo quality, Ovarian Sensitivity Index (OSI: number of oocytes retrieved/total Gonadotropins units × 1000), fertilization, implantation, and ongoing pregnancy rates. RESULTS: No significant difference was observed between the two groups regarding the total dose of gonadotropin used, OSI, and the number of total retrieved and mature oocytes. Grad A embryos and fertilization rate were significantly increased in group A. Implantation and pregnancy rates showed statistically insignificant changes. CONCLUSION: Treatment of poor responders with myo-inositol from one month before starting ICSI cycle continuing until ovulation trigger can improve fertilization rate and embryo quality, and may enhance the cumulative pregnancy rate in poor responders.