Comparison of progesterone protocol versus gonadotropin-releasing hormone antagonist protocol in terms of preventing premature LH surge and assisted reproductive technology outcome in infertile women: a randomized controlled trial.

INTRODUCTION: Progesterone can be used instead of GnRH agonists and antagonists in order to avert a premature LH surge during controlled ovarian stimulation (COS) protocol. Nonetheless, there is limited knowledge regarding its utilization. Thus, this study compared the effects of progesterone and GnRH antagonists (GnRH-ant) on premature LH surges and assisted reproductive technology (ART) results in infertile women undergoing ART. MATERIALS AND METHODS: In this clinical trial, the progesterone protocol (study group) and GnRH-ant protocol (control group) were tested in 300 infertile individuals undergoing IVF/ICSI. The main outcome was the number of oocytes retrieved. The secondary outcomes included premature LH rise/surge, the quantity of follicles measuring ≥ 10 and 14 mm, oocyte maturity and fertilization rate, the number of viable embryos, high-quality embryo rate and pregnancy outcomes. RESULTS: The study group exhibited a statistically significant increase in the number of retrieved oocytes, follicles measuring 14 mm or greater, and viable embryos compared to the control group (P < 0.05). The study group also increased oocyte maturity, chemical pregnancy rate, and clinical pregnancy rate (P < 0.05). Both groups had similar mean serum LH, progesterone, and E2 levels on trigger day. The control group had more premature LH rise than the study group, although this difference was not statistically significant. CONCLUSION: In conclusion, it can be stated that the progesterone protocol and the GnRH-ant protocol exhibit similar rates of sudden premature LH surge in infertile patients. However, it is important to note that the two regiments differ in their outcomes in ART. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT-ID: IRCT20201029049183N, 2020-11-27).

High Anti-Müllerian Hormone Strongly Correlates with Reproductive Outcomes in Women Undergoing Assisted Reproduction.

BACKGROUND: In a retrospective cohort of 881 women with gynecologic and unexplained infertility, we aimed to study the relationship between serum AMH levels and ART outcomes. This retrospective cohort includes 881 infertile women aged 20 - 45 who underwent their first fresh autologous non-preimplantation genetic diagnosis ART cycles between 2012 and 2020. METHODS: We assessed the correlation between AMH levels and reproductive outcomes among infertile women with different causes of infertility (including endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility). RESULTS: We found a strong correlation between high AMH levels and reproductive outcomes independent of age and the cause of infertility in women undergoing ART. In all patients with gynecologic and unexplained infertility, higher AMH correlated with the improved number of oocytes (p < 0.001), MII oocytes (p < 0.001), good-quality embryos (p < 0.001), chemical pregnancy rate (p < 0.001 in women < 37; and p = 0.002 in women over 37), clinical pregnancy rate (p < 0.05), and live birth rate (p = 0.05). CONCLUSIONS: Serum AMH concentrations can be invaluable for predicting ovarian reserve and reproductive outcomes in young and advanced-age infertile patients undergoing ART. However, it should not be used as the sole predictive marker for disqualifying infertile women from ART treatment. Further large cohort studies are warranted to determine an exact cutoff point for AMH to provide an accurate ART success prediction.

Investigating Ovulation Induction Outcomes in Patients with Decreased Ovarian Reserve Treated with Double Stimulation during The Follicular and Luteal Phases Compared to The Conventional Antagonist Cycle: A Randomized Clinical Trial.

BACKGROUND: It is difficult to obtain healthy oocytes in poor ovarian responders with conventional treatment methods. Thus, the need to investigate new methods is essential. This study aims to investigate ovulation induction outcomes in patients with decreased ovarian reserve (DOR) in two groups treated with double stimulation (DuoStim) during the follicular and luteal phases in comparison with the antagonist cycle. MATERIALS AND METHODS: This was a randomised clinical trial that enrolled the patients with reduced ovarian reserve. The patients referred for in vitro fertilization (IVF) at Molud Infertility Clinic, Ali Ebn Abitalib (AS) Hospital, Zahedan, Iran from 2020 to 2021. Participants were randomly divided into two groups, those who underwent treatment with DuoStim during the follicular and luteal phase (case group) and those who received the conventional antagonist cycle (control group). RESULTS: The mean number of metaphase II (MII) eggs was 7.7 ± 3.1 in the case group and 6.1 ± 3.9 in the control group (P=0.063). The mean total number of retrieved eggs in the case group was 9.2 ± 3.7 and in the control group, it was 6.9 ± 4.4 (P=0.023). The mean number of embryos obtained in the case group was 6.5 ± 3.9; in the control group, it was 4.7 ± 2.8 (P=0.016). CONCLUSION: The DuoStim method can effectively play a role in increasing the total number of retrieved eggs and embryos (registration number: IRCT20120817010617N8).

Beneficial effects of intraovarian injection of platelet-rich plasma in women with poor ovarian response.

OBJECTIVE: Infertility can result from a diminished ovarian reserve, but a potential remedy exists in the form of platelet-rich plasma (PRP) administration. This treatment involves both biological factors and tissue trauma mechanisms, which stimulate folliculogenesis, making it a promising and effective strategy. We assessed the impact of direct PRP injections into the ovaries on the fertility outcomes of women classified as poor responders. METHODS: A quasi-experimental study was conducted from April 2021 to December 2022, focusing on patients classified as POSEIDON grade 3 or 4. PRP injections were administered into both ovaries. After 3 months, data were collected on anti-Müllerian hormone (AMH) level, follicle-stimulating hormone (FSH) level, and the numbers of oocytes, mature oocytes, and good-quality embryos following ovarian stimulation. We then compared the data from before and after PRP injection. RESULTS: This study included 50 women, with a mean of 39 years (interquartile range [IQR], 35 to 43) and 4 years (IQR, 2 to 6) for age and infertility duration, respectively. FSH levels decreased after treatment, while AMH levels and the numbers of oocytes, metaphase II oocytes, and high-quality embryos increased. However, only the increase in high-quality embryos was significant. The pregnancy and spontaneous pregnancy rates were 20% and 14%, respectively. Notably, women with secondary infertility exhibited a significantly higher pregnancy rate than those with primary infertility. CONCLUSION: Ample evidence suggests that PRP can enhance ovarian function. However, further studies are needed to identify the appropriate candidates for this procedure, establish the optimal PRP preparation method, and standardize the procedure for its adjuvant use in assisted reproductive technology cycles.

The Effect of Altered Mucin1, FGF2, and HBEGF Gene Expression at The Ectopic Implantation Site and Endometrial Tissues in The Tubal Pregnancy Pathogenesis: A Case-Control Study.

BACKGROUND: Ectopic pregnancy (EP) is defined as implantation and development of an embryo outside of the uterine tissue. Women undergoing assisted reproductive technologies (ART), particularly frozen embryo transfer (FET), are in high-risk populations for EP. Mucin1 (MUC1), fibroblast growth factor-2 (FGF2), and Heparin-binding epidermal growth factor (HBEGF) genes are involved in the endometrial receptivity pathway, leading to normal eutopic implantation; Although, their relevance in the tubal pregnancy after FET is unknown. We aimed evaluation of Mucin1, FGF2, and HBEGF expression fold as endometrial receptive markers in the EP patients following the FET cycle. MATERIALS AND METHODS: A case-control study was conducted on ten patients (five EP patients and five women in the pseudo-pregnancy group, as the control samples). Pseudo-pregnancy group was established in women who were candidates for hysterectomy for benign diseases. Fallopian tube biopsies and corresponding endometrial tissues from these patients were taken during the hysterectomy. However, the fallopian tube and endometrial tissues of EP patients were obtained during salpingectomy. The mRNA expressions of Mucin1, FGF2, and HBEGF genes in the fallopian tube and endometrial tissues were measured by real-time polymerase chain reaction (PCR) assay. RESULTS: MUC1 mRNA expression level in the endometrium of the case group was higher than in the control group (P=0.04); however, its mRNA expression in the fallopian samples of the case group in comparison with the control group was significantly decreased (P=0.001). The HBEGF mRNA expression level was not significantly different between the case and control endometrium, whereas its expression was significantly increased in the case fallopian samples compared with the control ones (P=0.001). The same pattern was observed for FGF2 mRNA expression level in the fallopian samples of the case group but was significantly reduced in the endometrial samples in comparison with the control samples (P=0.03). CONCLUSION: Mucin1, FGF2, and HBEGF gene mRNA expression changes may explain the embryo rejection from the uterus and the establishment of a receptive phenotype in fallopian cells.

The Effect of Palm Pollen and Black Seed Pollen on Male Sex Hormones and Sperm Quality: A Single-Blind, Placebo-Controlled Clinical Trial Study.

BACKGROUND: Nowadays, using medicinal properties is a good alternative for infertility treatment to use them is increasing in the world. The aim of this study was to determine the effects of Herbal oral capsules included palm pollen extract (DPP) and Nigella Sativa extract (NS) on sex hormones in adult infertile men. MATERIALS AND METHODS: In this a single-blind, placebo-controlled clinical trial study, a total of 62 infertile men between 22 and 42 years of age were randomly selected and tested for sex hormones and prolactin. Thirty people in the case group received two 500 mg/kg capsules on a daily basis containing an herbal composition of palm pollen extract (350 mg) and black seed powder extract (250 mg) and the 20 in the control group received a placebo in the morning and at night for 3 months. The herbal composition capsules were manufactured by the Golbadistan Company. At the end of the three -month period, blood and semen tests were performed before and after the intervention in the case group that was compared with the control group. Hormonal assays were performed by Immunoradiometric Assay (IRMA) method. The data entered SPSS statistical software and the level of significance was set at P≤0.05. RESULTS: The spermiogram test results showed significant changes in the sperm count, progressive motility and rapid progressivity of the case group at the end of a quarterly period after consuming plant composition except for morphology (P=0.001, P=0.001, P=0.02, P=0.23). In addition, in the case group, the concentration of testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) was significantly increased compared to the control group (P=0.000, P=0.004, P=0.012). CONCLUSION: It seems that taking one 500 mg/kg capsule of DPP and NS extract can significantly increase sperm parameters and testosterone (registration number: IRCT2015020120895N1).

Expressions of vascular endothelial growth factor A, mucin-1, colony-stimulating factor-1, heparin-binding epidermal growth factor-like growth factor, and fibroblast growth factor 2 genes in the female reproductive tracts of women with ectopic pregnancy: A case-control study.

Background: Ectopic pregnancy (EP) is defined as embryo implantation in a location other than the uterine cavity. Objective: We aimed to evaluate the expression of several genes, which may play a role in EP, in the ampulla region of fallopian tubes and endometrial tissue of women with EP. Materials and Methods: In this case-control study, 5 women who underwent salpingectomy due to EP, comprised the 5 pseudo-pregnant women as a control group. These participants referred to the Royan Institute, Shariati, and Arash hospital, Tehran, Iran during 2019-2021. We evaluated the expressions of vascular endothelial growth factor A, mucin-1, colony-stimulating factor-1, heparin-binding epidermal growth factor-like growth factor (HBEGF), and fibroblast growth factor 2 genes in the fallopian tube and endometrium of EP cases by real-time polymerase chain reaction using specific primers. Results: The vascular endothelial growth factor expression was significantly higher in the ampulla region of the controls. However, no significant differences were observed in endometrial tissue. Assessments of colony-stimulating factor-1 and fibroblast growth factor 2 showed no significant differences between the case and control groups. HBEGF showed significantly higher expression in the ampulla region of EP cases, but no significant difference was observed in HBEGF expression in the endometrial tissues of the study groups. Mucin-1expression was significantly higher in both study regions of the EP cases. Conclusion: Our results have strongly suggested that these genes play important roles in proper implantation, and disruptions in their expression patterns could lead to EP. However, more studies are needed to confirm the current findings.

The effect of intrauterine hCG injection before embryo transfer on pregnancy rate in frozen embryo transfer cycles.

Objective: HCG (human chorionic gonadotropin), which is secreted by cytotrophoblast cells, plays an important role in improving pregnancy outcomes among patients with infertility or related problems. In this study, we evaluate the effect of intrauterine hCG injection prior to frozen embryo transfer on pregnancy outcomes. Methods: In this clinical trial study, among women with infertility problems referred to (XXX) and those with frozen embryos were included in the study. 155 patients in the intervention group received 500 units of hCG while 157 in control group received saline prior to embryo transfer. Along with demographic data, successful in vitro fertilization and clinical pregnancy, loss of pregnancy, successful transplantation, and biochemical parameters were compared among the two groups. Results: The mean age of the patients included in the study was 32.97 ± 3.31 years. The level of anti-Mullerian hormone, follicle stimulating hormone and the grade of frozen embryos were not significantly different between the two groups (P > 0.05). The rate of laboratory pregnancy in the intervention group was significantly higher than in the control group (51% vs 35%), p = 0.006. The rate of successful implantation and clinical pregnancy in the intervention group was also significantly higher, p = 0.01 and p = 0.006, respectively. Overall loss of pregnancy in intervention group was 78.1% and 86.0% in control group which was not significantly different, p = 0.068. Conclusion: The outcomes of our study showed that 500 IU of hCG prior to embryo transfer improves the rate of clinical and laboratory pregnancy. However, it does not reduce the rate of loss of pregnancy. Further studies are therefore required in this area.

Role of soap and water in the treatment of wound dehiscence compared to normal saline plus povidone-iodine: A randomized clinical trial.

BACKGROUND: The incidence of cesarean section is increased. About 3-30% of the women who undergo cesarean experience surgical site infections (SSIs). Many methods, have been used to decrease the incidence of SSIs, but despite much effort, no definite efficacious method has been suggested. MATERIALS AND METHODS: In this parallel, single-blinded, randomized control trial, 56 women with post-surgical superficial wound dehiscence were divided into two groups in a 1:1 ratio. One group was irrigated with normal saline for irrigation and Firooz® baby soapand the other with normal saline for irrigation and povidone-iodine. Formation of granulation tissue was monitored in both groups. Also, the reason for surgery, length of wound dehiscence, and duration of hospitalization and wound union after were compared in both group's. RESULTS: The soap group patients were irrigated for 4.18 ± 1.96 days compared to 5.36 ± 2.83 days for the patients in povidone-iodine group (P = 0.414). The granulation tissue was formed after 3.88 ± 1.94 days in the soap group compared to 4.48 ± 2.92 days in the other group (P = 0.391), and the duration of hospitalization was 5.48 ± 2.04 days in the soap group compared to 6.3 ± 2.95 days in the other group (P = 0.423). So, no differences were observed between the two groups. CONCLUSION: It can be concluded since there is no difference between the results of two groups, irrigation with normal saline and soap is safe, easy and causes no harm or allergy compared with povidone iodine and normal saline.

Effectiveness of hysteroscopic repair of uterine lesions in reproductive outcome.

BACKGROUND: Small intrauterine lesions such as septum, adhesion, polyp, and submucous myoma may be of greater significance in causing implantation failure, poor reproductive performance and abnormal uterine bleeding. We studied effectiveness of therapeutic intervention through operative hysteroscopy in improvement of pregnancy outcome and cessation of abnormal uterine bleeding (AUB) in women with pregnancy and fertility problems. MATERIALS AND METHODS: This prospective cohort study was performed between 2003- 2009 on 65 patients with primary or secondary infertility, recurrent abortion and structural uterine lesions reported in sonography or hysterosalpingography. After hysteroscopic metroplasty, myomectomy, adhesiolysis and polypectomy under laparoscopic guide, we evaluated reproductive outcome, early and late complications, one year after surgery. RESULTS: Among all patients with recurrent abortion, 6 patients (75%) complete their pregnancy successfully. Our results showed that pregnancy rate after metroplasty was 58%. Reproductive outcome was poor after myomectomy and adhesiolysis. Abnormal uterine bleeding was improved in 62% of patients. CONCLUSION: Structural uterine lesions has been assumed to cause infertility, while several studies have shown very poor reproductive performance with high miscarriage and low term delivery rates when malformation is not treated. We show improvement in conceptional outcome and in patient's chief complaints after hysteroscopy surgery of these anomalies.

Comparison study on effectiveness of pentoxifyllin with LD to prevent recurrent endometriosis.

BACKGROUND: About 75% of the symptomatic patients who involved with endometriosis have pelvic pain and dysmenorrhea. Pentoxifyllin is one of the drugs that according to its mechanism could be effective for pain relief of endometriosis which has been used for endometriosis treatment recently. OBJECTIVE: We conducted a comparative study for detecting the effect of pentoxifylin (as an immonomodelator) in preventing recurrence endometriotic pain with pentoxifylin plus a combined contraceptive pill with low dose estrogen (LD) and also the LD pill alone. MATERIALS AND METHODS: This was a comparative clinical trial on 83 patients with the chief complaint (CC) of pain (dysmenorrheal /or pelvic pain) and with the end diagnosis of endometriosis, in an operative laparoscopy. Patients, dividing to 3 groups, were treated with pentoxifylin, pentoxifylin+LD and LD alone for 10 months. The severity of pain (dismenorhea and/or pelvic pain) was detected by visual analogue scale (VAS) before and after the treatment. The severity of endometriosis in the patients was: I in class I and II in class II and III in class III. The groups were matched for the pain. The number of the patients in group 1, 2 and 3 were 28, 28 and 27 respectively. RESULTS: The pain was reduced in the groups of pentoxifylin+LD (p<0.001) and LD alone (p=0.00). The pain relief was not significant in the group of pentoxifylin alone (p=0.136). After treatment, the severity of pain was not significantly different between the LD group and the LD+penthoxyfillin group, but there was difference between these two groups and the group of penthoxyfillin alone. CONCLUSION: This study showed that penthoxyfillin actually could not have any effect on the pain relief of endometriosis. It also made it clear that penthoxyfillin could not increase the efficacy of LD when used with this medication.

Assessment of the diagnostic capability of serum creatine phosphokinase and its isoenzyme in ectopic pregnancy.

BACKGROUND: Our goal was to assess the diagnostic value of creatine phosphokinase (CPK) and its isoenzyme CPK- muscle brain (MB) in ectopic pregnancy (EP) in order to locate a simpler diagnostic approach for EP. MATERIALS AND METHODS: This was a prospective study that performed consecutive sampling for 20 months in two major hospitals in Isfahan, Iran. All pregnant patients in their first trimester of gestation that presented with complaints of vaginal bleeding, abdominal pain, or both enrolled in this study. Blood sampling was performed for laboratory analyses (CPK, CPK-MB). After their diagnosis was established, patients were put in either the EP or non-EP group. We used SPSS software version 10 for data analysis, diagnostic parameters were determined, and a relative operating characteristic (ROC) curve was plotted for each biochemical marker. RESULTS: A total of 106 patients, 53 in the EP group and 53 in the non-EP group enrolled in this study. The results for CPK were as follows: sensitivity (69.81%), specificity (64.15%), positive predictive value (PPV; 66.07%), negative predictive value (NPV; 68%), positive likelihood ratio (PLR) (1.95), and negative likelihood ratio (NLR) (0.49). The results for CPK-MB were: sensitivity (71.7%), specificity (56.6%), PPV (62.29%), NPV (66.7%), PLR (1.65), and NLR (0.5). The area under the ROC curve for CPK was 0.692 and for CPK-MB it was 0.647. CONCLUSION: Although we have observed a significant elevation in CPK and CPK-MB serum levels in EP, transvaginal ultrasound (TVS) is still the better diagnostic tool for EP.