E ndometrial thickness (ET) is one of the best predictors of implantation rate and pregnancy success rate because endometrial growth depends on hormones. Estrogen regulates the proliferative phase, endometrial proliferation induced by estrogen after menstruation is largely dependent on blood flow to the basal endometrium that produces progesterone receptors which are required for progesterone-regulated endometrial growth in the secretory process. To compare the effect of estradiol valerate vs. sildenafil citrate on endometrial receptivity and subsequent pregnancy outcome in unexplained infertility patients receiving letrozole for ovulation induction. Herein, 21 patients with unexplained infertility underwent ovulation induction by letrozole (2.5 mg). Patients were divided into 2 groups; group A (10 patients) were given sildenafil tablets vaginally (25 mg) four times daily and group B (11 patients) were treated with estradiol valerate tablet 2 mg/12 hours. Patients were evaluated by transvaginal ultrasonography (TVS) to determine endometrial thickness, pattern, size, and the number of the dominant follicles, serum assessment of Vascular Endothelial Growth Factor (VEGF) level at trigger day, and chemical pregnancy outcome 14 days later. Results showed that the endometrial thickness, patterns of the endometrium, VEGF, size of the dominant follicle at the trigger day, and pregnancy rates were not significantly different between the two groups. However, the difference in the number of the dominant follicles at trigger day was statistically significant which is more in the sildenafil treated group. The present study confirmed the findings of both Sildenafil and E 2 valerate to boost endometrial receptivity and pregnancy rate.
Glycotoxins termed as advanced glycation endproducts (AGEs) are made endogenously and exogenously. Maillard reaction is a chemical non-enzymatic process, between sugars and a free amino acid group of nucleic acids, proteins, and lipids which happens exogenously when handled with high temperature for a prolonged period and in a dry environment, resulting in glycotoxins (AGEs) formations. This reaction is responsible for the taste, color, and smell of food. Glycotoxins derived from food are absorbed in the intestine and store in cells and tissues. Also, glycotoxins are derived exogenously from smoking. While endogenous glycotoxins are generated by normal body physiology. Obesity and insulin resistance may induce glycotoxins (AGEs) accumulation. The objective of this study was to evaluate the relationship between glycotoxins (AGEs) and obesity. 66 infertile females who were undergoing intracytoplasmic sperm injection ICSI. These females were classified into three groups according to their body mass index. On the day of ova pick up the collect serum and follicular fluid for subsequent measurement of glycotoxins (AGEs) by ELISA kits. there was a significant difference in the concentration of glycotoxins in follicular fluid and serum between the three ICSI groups of patients. As well as there was a significant difference in the concentration of glycotoxins (AGEs) in follicular fluid and serum in the same ICSI groups of patients. there is a significant positive relation between glycotoxins (AGEs) and increase BMI.
Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility and is associated with an increased risk of premature luteinizing hormone (LH) surges during controlled ovarian stimulation. Progestin-primed ovarian stimulation (PPOS) using Medroxyprogesterone Acetate (MPA) has emerged as a convenient alternative to conventional gonadotropin-releasing hormone (GnRH) antagonist protocols. This study aimed to compare the effects of MPA-based PPOS and GnRH antagonist protocols on oocyte yield, maturation, fertilization, and embryo quality in women with PCOS undergoing ICSI . This prospective, randomized, open-label controlled clinical trial included 108 women with PCOS undergoing ICSI at the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies, Al-Nahrain University, Baghdad, Iraq, between 2023 and 2024. Participants were allocated to an MPA-based PPOS group (n=49) or a flexible GnRH antagonist group (n=59). Oocyte yield, metaphase II (MII) oocytes, fertilization rate, embryo quality, ovarian sensitivity index (OSI), gonadotropin consumption, stimulation duration, and LH profiles were evaluated.No significant differences were observed in baseline characteristics or hormonal profiles between groups. The MPA group showed a numerically higher number of retrieved oocytes (20.65 ± 7.50 vs. 13.39 ± 4.41; p=0.083) and MII oocytes (15.10 ± 5.20 vs. 11.24 ± 4.12; p=0.09), although these differences were not statistically significant. Fertilization rates were comparable between groups (72.4 ± 10.6% vs. 71.2 ± 11.3%; p=0.68), as were embryo quality, OSI, gonadotropin consumption, and stimulation duration. Both protocols effectively suppressed premature LH surges without premature ovulation or cycle cancellation. MPA-based PPOS appears to be an effective and practical alternative to GnRH antagonist protocols for PCOS patients undergoing ICSI, providing comparable fertilization and embryological outcomes with effective LH suppression. Its oral administration and potential cost advantages may be particularly valuable in resource- limited ART settings.
Various types of anesthetic techniques were described for oocyte recovery. Different anesthetic agents have been used with different effects on oocyte quality and embryonic development and studies on the potential toxicity of general anesthesia ended up with conflicting results. Many experiments as well as human studies documented the existence of anesthetic agents in the follicular fluid (FF) with possible adverse effects on the oocyte quality and subsequent embryo development. Ketamine and remifentanil were used for the studied groups to compare oocytes and embryos characteristic of infertile women during oocytes retrieval under general anesthesia: one group receiving ketamine, midazolam, and propofol and the other group receiving remifentanil, midazolam and propofol. 60 infertile females were undergoing intracytoplasmic sperm injection categorized in two groups, group I received midazolam, remifentanil and propofol; whereas, group II received midazolam, ketamine and propofol. There was highly significant difference in mean abnormal oocyte between ketamine and remifentanil groups. Grade III embryos were significantly limited to ketamine group. FF ketamine and remifentanil were not significantly correlated to any of oocyte characteristics or embryo characteristics. Anesthetic agents, ketamine and remifentanil, were detected in the FF of infertile women and within recommended doses. Ketamine resulted in adverse effects on oocyte and embryo quality in comparison with remifentanil represented by greater percentage of abnormal oocytes and that bad quality embryos were limited to ketamine group.
The luteal phase (LP) in the fresh ICSI cycle is insufficient, adequate LP support is one of the approved treatments for improving implantation and pregnancy rates. It is generally known that the LP is inadequate after ovarian stimulation due to negative from supra-physiological blood levels of steroids released by numerous corporal luteal, LH concentrations are low during the luteal phase. In this study, patients were divided into two groups: (40) patients as study group; those who received GnRHa (Decapeptil 0.1 mg), three days after embryo transfer, in addition to conventional luteal phase support (LPS) in the LP to increase the implantation and pregnancy rate in IVF; and their control group (40) received standard LPS only. On the second day of stimulation, blood samples for FSH, LH, TSH, E 2 , and prolactin were taken. On the day of ovulation induction, measure E 2 , progesterone, and LH; and on the day of embryo transfers, measure progesterone and LH. The overall characteristics of the patients in both groups were not significantly different. There was also no significant change in the number of total oocytes, mean of metaphase II oocytes percent, cleavage rate, grade I embryo percent, or serum hormones level between the study and control groups (p > 0.05). GnRH agonist treatment in the luteal phase improves clinical pregnancy and implantation rate in fresh ICSI cycles but is not statistically significant.
Hyaluronic acid (HA) is an anionic, non-sulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. The study included 40 infertile females. A full history taking, complete general examination, complete gynecological examination, and infertility workup including basal hormonal analysis, and uterine cavity assessment by ultrasound and tubal patency evaluation by hysterosalpingogram was done in addition to husband’s seminal fluid analysis. The control group did not receive any ovarian stimulation drugs, while the 2 nd group was treated with letrozole + gonadotropin. The ovarian stimulation protocol was chosen for each patient according to her age, history, and hormonal assay. Evaluation of thickness and pattern of the endometrium, size, and the number of mature follicles was performed by transvaginal ultrasonography on the 2 nd day of the menstrual cycle and cycle day 11-14 before hCG injection. The study showed no correlation between HA and LH at triggering day in women who received letrozole plus Gonadotropin but a positive correlation was documented between HA concentration and E 2 in addition to a positive correlation with progesterone, the number of follicles, and endometrial thickness at the day of triggering of ovulation. The study revealed that mean hyaluronic acid concentration was elevated significantly (P<0.05) in pregnant women after stimulation protocol compared with nonpregnant (164.2 vs. 152.1 pg/ml). HA was significantly higher in women who undergo ovarian stimulation with letrozole which was a good protocol in the treatment of women with ovulatory problems.
Reactive oxygen species (ROS) are active chemical compounds created by the body's metabolic process and are crucial in human reproduction. Excessive ROS can contribute to oxidative stress, which has been linked to poor fertility. Embryo culture medium plays an essential role in IVF/ICSI cycles. Eighty participants underwent ovarian stimulation and ICSI cycles; ROS levels were measured in blood samples on the ovum pickup (OPU) day and in each embryo culture dish on ET day using enzyme-linked immunosorbent assay (ELISA). These values were associated with the quality of generated embryos. Women were divided into two groups; the first had day three embryo transfers, whereas the second received blastocyst transfers on day 5. Grades I embryo count was shown to be inversely related to the serum and culture medium ROS levels. Pregnant women had significantly greater levels of GI embryos (p=0.011) and lower levels of GIII embryos (p=0.024). Pregnancy rates for the third-and fifth days of the embryo transfers were 24% and 50%, respectively, with (p=0.045). Pregnancy success rates were increased after ET day five and were strongly influenced by transfer day. Blastocyst-stage embryos with high serum ROS levels were found to be underdeveloped. Culture medium ROS levels can be used as an adjuvant criterion for embryo selection and metabolic marker for developing embryos.
CA125 is a glycoprotein mucins (MUC16) tumor marker, used in screening, ovarian and endometrial malignancies and in monitoring therapy, early recurrences, and prognosis of these cancers. Hormonal induction for ovulation can elevate the risk of ovarian cancers so CA125 may be used for screening in PCOS as an unsafe group and the way of treatment may need to be changed in these patients. Polycystic Ovarian Syndrome (PCOS) is one of the most common hormonal disturbed diseases that can affect females in reproductive life. It has both metabolic and fertility impacts that can be seen in the reproductive period and post-menopausal life. To study the correlation between PCOS and CA125 level in relation to body weight in non-cancerous patients. 60 women were selected with age 18-42-year-old forty of them were diagnosed with PCOS according to Rotterdam criteria. They were divided into two groups according to BMI G1 was more than 25 kg/m 2 (overweight and obese) G2 was less than 25 kg/m 2 (normal) and the G3 was 20 healthy non-PCOS BMI less than 25 kg/m 2 . Blood samples were taken in the early follicular phase for assessing luteinizing hormone (LH), follicular stimulating hormone (FSH) and, free testosterone (FT) hormone. Other blood samples were taken at the late follicular phase to measure CA125 levels using Enzyme-Linked Immune Sorbent Assay (ELISA). PCOS G2 were significantly higher in the concentration of CA125 than PCOS G1 (p< 0.05), but there was no significant difference in CA125 level in groups when there is no significant difference in body mass index (BMI) between PCOS G1 and G2. P>0.05. The negative relation between CA125 concentration and weight. The tumor marker CA125 efficacy is decreased in obese women. Furthermore, PCOS not causes an increase in CA125 in the non-cancerous patient.
Pregnancy-Associated Plasma Protein (PAPP-A) is a zinc metalloproteinase in the insulin growth factor system (IGFs) produced by the syncytiotrophoplast region of the placenta. It plays a critical function in the cleavage of IGFBP4. In the ovary IGFs, it regulates follicular and oocyte maturation, and steroidogenesis. While in polycystic ovarian syndrome (PCOS) Hyperinsulinemia and hyperandrogenemia it causes follicular environment changes and early ovulation resulting in lower oocyte and embryo quality in patients and this will decrease the success of pregnancy in women enrolled in the ICSI cycle. The present study aimed to assess the relationship of PAPP-A levels in serum and follicular fluid in women with PCOS and non-PCOS with oocyte and embryo quality in women undergoing ICSI cycle. 45 infertile Iraqi women were enrolled. Women with PCOS had to meet at least two of the three criteria set by the Rotterdam ESHRE/ASRMS criteria, the age of the included women ranged between 20-45 years. In non-PCOS patients, PAPP-A has higher level in serum and follicular fluid but without a statistically significant difference matching with PCOS group. In addition, there was no significant correlation between PAPP-A levels in serum and follicular fluid with oocytes and embryo characteristics. However, PAPP-A levels are higher in serum and follicular fluid in women with positive pregnancy but without significant differences. PAPP-A had no correlation with oocyte and embryo quality.
There is a relation between adipose tissue and macrophages. These macrophage cells influence adipose tissue by releasing many bioactive chemicals, including the wingless-type MMTV integration site family 5a (wnt5a) glycopeptides and the more traditional cytokines. Healthy adipocytes can release the wnt5a inhibitor Secreted frizzled-related protein 5(SFRP5). However, this protective effect was found to be reduced in obesity. This study aimed to assess the effect of follicular and serum levels of SFRP5 as well as serum and follicular levels of wnt5a on ICSI outcome and determine the potential roles of SFRP5 as a predictor of positive pregnancy in Iraqi infertile females undergoing ICSI with different body mass index .Ninety infertile females who received intracytoplasmic sperm injection and had various infertility factors between 18 and 45 years participated in this prospective clinical cross-sectional study. Follicular fluid, serum SFRP5, and serum and follicular fluid wnt5a levels were measured for all participants on the day of ovum pickup. In addition, ICSI outcomes were determined. There was a significant difference in the mean total gonadotrophin dose used among the three studied groups (p = 0.023), higher in overweight and obese females than normal-weight females. There was a positive significant correlation between serum plus follicular fluid wnt5a and total gonadotropin dose. Serum and follicular fluid SFRP5 levels were significantly higher in normal-weight females. There were higher serum (p-value=0.002) and follicular fluids (p-value=0.005) SFRP5 levels in pregnant females. Both SFRP5 and wnt5a glycoproteins were detected in infertile women's serum and follicular fluid. Serum and follicular fluid secreted frizzled-related protein 5 level positively associated with ICSI outcome. The cutoff values for serum and follicular fluid SFRP5 were ≥15.86 (ng/ml) and ≥ 11.3(ng/ml), respectively, as predictors of positive pregnancy in women undergoing IVF/ICSI cycles. Obesity, BMI, SFRP5, wnt5a, ICSI Outcome