Corrigendum to "The effect of intrauterine human chorionic gonadotropin injection before embryo transfer on the implantation and pregnancy rate in infertile patients: A randomized clinical trial" [Int J Reprod BioMed 2016; 14: 657-664].

[This corrects the article on p. 657 in vol. 14.].

Fresh embryo transfer in the cleavage and blastocyst stages and pregnancy outcomes: A retrospective cross-sectional study.

Background: Advances in cell culture media have led to a trend of embryo transfer from the early cleavage stages to blastocyst stage. Objective: The study aims to compare the effects of fresh embryo transfer in cleavage and blastocyst stage on pregnancy outcomes. Materials and Methods: This cross-sectional study was conducted on 1422 cases referred to the Umm-al-Banin Infertility Clinic Center, Dezful, Iran, between July 2013 and December 2020 who were candidates for in vitro fertilization/intracytoplasmic sperm injection for fresh embryo transfer. A total of 1246 cases were divided into 4 categories on days 2-5 or 6. Chemical and clinical pregnancy, abortion, multifetal pregnancy, ongoing pregnancy, and live birth rates were analyzed. Results: Fresh embryo transfer was performed in 28.5% of the cases on the 2nd day, 45.8% on the 3rd, 15.3% on the 4th day, and 10.4% on days 5 or 6. The overall clinical pregnancy and live birth rates were estimated at 20.6% and 17.6% in the cleavage, and 17% and 14% in the blastocyst stages, respectively. However, no significant difference was observed in either group. In addition, there was no significant difference between groups in terms of the abortion, multifetal pregnancy, and ongoing pregnancy rate (p > 0.05). Conclusion: According to the results, the consequences of pregnancy in fresh embryo transfer at the blastocyst stage were not superior to embryo transfer at different stages of the cleavage process.

Changes of Serum Level of Homocysteine and Oxidative Stress Markers by Metformin and Inositol in Infertile Women with Polycystic Ovary Syndrome: A Double Blind Randomized Clinical Trial Study.

Background: Hyperhomocysteinemia plays an important role in the anovulation in infertile women suffering from polycystic ovary syndrome (PCOS). However, long-term metformin therapy elevated homocysteine (Hcy) concentration in these individuals. Inositol increases serum insulin levels and improves ovulation. The aim of this study was to compare the effect of metformin and inofolic on the level of serum Hcy and oxidative markers in the infertile patients with PCOS. Materials and Methods: Eighty PCOS infertile women undergoing in vitro fertilization in the Umm-al-Banin clinical center, Dezful, Iran from December 2018 to September 2019 were invited to participate in this double blind randomized clinical trial. They were divided into two groups; group A who received metformin (1000 mg twice/day) and folic acid (400 µg /day) and group B who used inofolic (inositol+ olic acid 200 µg twice/day) for 3 months. Results: The mean Hcy levels increased significantly by metformin (P=0.02), but not by inofolic. There was a decrease in the total antioxidant capacity (TAC) after metformin administration (P=0.01). In both groups, a significant increase in folic acid levels was observed after treatment (P=0.04). Also, no significant change in vitamin B12 and malondialdehyde levels was observed in both groups (P=0.08). Conclusion: These findings indicate an increase in the serum Hcy levels as well as a remarkable decrease in TAC following metformin treatment. Given the rise in blood Hcy in PCOS patients, inofolic and other medications containing inositol can be prescribed instead of metformin (registration number: IRCT20190508043516N1).

Comparison of Follicular Fluid Paraoxonase 3 Level, Ovarian Hormones and Oocyte Quality between Fertile and Infertile Women.

Background: The purpose of the current study was to evaluate the possible effect of follicular fluid paraoxonase 3 (PON 3) on oocyte quality and sex hormones. Methods: This descriptive-analytical study was performed on totally 90 enrolled women including fifty infertile women presenting with polycystic ovaries and uni-lateral tubal factor and forty fertile women with male factor infertility referring to Umm-al-Banin Infertility Clinic in Dezful, Iran for in vitro fertilization during October 2018 to November 2019. Oocyte removal was carried out under transvaginal ultrasound guidance, and follicular fluid (FF) was removed and preserved to detect PON3, estrogen, and progesterone levels. In addition, oocyte number and quality were assessed and its association with PON3 activity in the FF was evaluated. Oneway ANOVA and Fisher's least significant difference (LSD) were used for data analysis and p≤0.05 were considered statistically significant. Results: A significant increase was observed in the total number of the oocytes and mature metaphase II oocytes with ≥20 pg/ml of PON3 concentration in the FF (p≤0.05). Moreover, a positive relationship was shown between the increased estradiol level in follicular fluid and PON3, so that the highest estradiol level was observed in the amount of 31-40 pg/ml of PON3 (p≤0.05). Conclusion: According to the results, as the number of the mature oocytes increased, the amount of PON3 as well as estradiol levels in the FF increased. This research displays an increase in the level of PON3 with mature oocytes, thus supporting the indirect evidence for the function of PON3 in follicle development.

Follicular Fluid Zinc Level and Oocyte Maturity and Embryo Quality in Women with Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is considered to be one of the most common endocrine disorders in women of reproductive age. Zinc, a vital trace element in the body, plays a key role in maintaining health, especially due to its antioxidant role. On the other hand, lack of antioxidants and oxidative stress can adversely affect oocytes quality and consequently fertility rate. The available studiesthat report the effect of follicular fluid (FF) zinc in terms of the number and quality of the oocytes in infertile women with PCOS, are few and not consistent. We decided to investigate this issue. MATERIALS AND METHODS: In this cross-sectional study, from the women with PCOS referring to Omolbanin Hospital, Dezful, Iran (February to December 2019), a total of 90 samples (follicular fluid, oocytes, and embryos) were collected from those who had undergone in vitro fertilization (IVF). To measure zinc level in follicular fluid, high performance liquid chromatograpy (HPLC) was utilized. Also, oocytes maturity and embryos quality evaluation was performed using inverted optical microscopy. One-way ANOVA and Fisher's least significant difference (LSD) were used for data analysis. RESULTS: The amount of FF zinc was not associated with any significant differences in the number of oocytes and metaphase I (MI) and germinal vesicle (GV) oocytes, but a significant decrease was observed in the number of metaphase II (MII) oocytes at zinc values lessthan 35 µg/dL. The FF zinc levels lessthan 35 µg/dL were also significantly associated with decreased embryo quality. CONCLUSION: A significant relationship was found between the level of FF zinc and the quality and the number of oocytes taken from the ovaries of infertile patients with PCOS history who were candidates for IVF treatment as well as the number of high quality embryos.

The effect of follicular fluid selenium concentration on oocyte maturation in women with polycystic ovary syndrome undergoing in vitro fertilization/Intracytoplasmic sperm injection: A cross-sectional study.

BACKGROUND: A high level of free radicals and oxidative substances in women with polycystic ovary syndrome (PCOS) can affect the ovaries through oxidative stress. Antioxidants such as selenium, a vital trace element in human health, can improve the prognosis of PCOS by reducing oxidative stress. OBJECTIVE: This study was performed due to the lack of comprehensive information about selenium concentration in follicular fluid and its effect on the oocyte count and quality in infertile women with PCOS. MATERIALS AND METHODS: In this cross-sectional study, 78 women with PCOS referred to Umm-al-Banin Infertility Clinic Center, Ganjavian Hospital, Dezful, Iran for in-vitro fertilization from March to November 2019 were enrolled. After ovarian stimulation with the antagonist protocol, the oocytes were retrieved under transvaginal ultrasound in in-vitro fertilization/intracytoplasmic sperm injection cycles, and selenium concentrations were measured in the follicular fluid using an atomic absorption method by spectrophotometer device. Oocyte count and morphology were evaluated using inverted optical microscopy. RESULTS: There were no significant differences between follicular fluid selenium concentrations in terms of the total number of oocytes and immature oocytes in the metaphase I and germinal vesicle stages. However, a significantly reduced number of metaphase II oocytes was observed at selenium levels < 40 µg/dL (p = 0.001). CONCLUSION: Based on our results, low levels of follicular selenium concentration in infertile women with PCOS can reduce the quality and potency of oocyte maturation.

Effect of embryo transfer depth on IVF/ICSI outcomes: A randomized clinical trial.

BACKGROUND: Although there has been remarkable advancement in the field of assisted reproductive technology, implantation failure remains a significant issue in most infertile couples receiving these treatments. Embryo transfer is important in assisted reproductive technology and directly affects the implantation rates and pregnancy outcomes. OBJECTIVE: To assess the effect of two different distance embryo transfer sites from fundal endometrial surface on the outcomes of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. MATERIALS AND METHODS: A total of 180 women who were candidate for IVF/ ICSI/ embryo transfer in Yazd Research and Clinical Center for Infertility were equally assigned to two groups based on the distance between the fundal endometrial surface and catheter tip to investigate implantation, chemical and clinical pregnancy (group A: 15 ± 5 mm and group B: 25 ± 5 mm, respectively). RESULTS: The subjects in the group B showed significantly higher implantation rate, chemical and clinical pregnancy rate compared to the group A (p = 0.03, 0.01, 0.04, respectively). The rate of ongoing pregnancy and miscarriage indicated no significant differences between groups (p = 0.21, 0.27, respectively). CONCLUSION: In conclusion, our study showed that the depth of embryo replacement inside the uterine cavity at a distance of 25 ± 5 mm beneath fundal endometrial surface have better effects on the pregnancy outcomes of IVF/ICSI cycles and can be considered as an important factor to improve the success of IVF cycles.

Level of Bisphenol A in Follicular Fluid and Serum and Oocyte Morphology in Patients Undergoing IVF Treatment.

Objective: To assess the correlation between the levels of BPA in the serum and follicular fluid (FF) using oocyte morphology. Materials and methods: In this cross-sectional research, oocyte, FF, and serum samples were obtained from a sample population consisting of 90 women undergone in vitro fertilization in Ganjavian Hospital in Dezful, Iran during October 2017-March 2018. The ELISA kit was utilized for the measurement of the BPA levels. In addition, oocyte morphology simultaneous with inverted optical microscopy. Results: Follicular fluid BPA levels had no significant effect on MII oocytes (p ≥ 0.05). However, the mean levels of degenerated oocytes and germinal vesicle (GV) were significantly higher in the women with high BPA levels in the FF (p ≤ 0.05). Moreover, the mean counts of MII oocytes and oocytes were significantly higher in the women with serum BPA levels of ≤ 50 ng/ml (p ≤ 0.05), while the mean count of GV oocytes was significantly higher in the women with serum BPA levels of ≥ 150 ng/ml (p ≤ 0.05). Conclusion: According to the results, higher FF BPA levels were associated with the higher counts of GVs and oocytes, while oocytes with higher maturity can be achieved in lower levels of BPA in the serum of patients.

The effect of intrauterine human chorionic gonadotropin injection before embryo transfer on the implantation and pregnancy rate in infertile patients: A randomized clinical trial.

BACKGROUND: Implantation is one of the essential steps for the success of assisted reproductive techniques (ART). Their success depends on three main factors: embryo quality, endometrial receptivity (ER), and synchrony between embryo and endometrium. There are various factors that regulate the complex process of implantation. In this regard, one may refer to human chorionic gonadotropin (hCG) as the most important factor. OBJECTIVE: This study aims to investigate the effect of intrauterine hCG injection before embryo transfer (ET) on pregnancy outcome in infertile couples. MATERIALS AND METHODS: A total of 159 patients undergone In vitro Fertilization/ Intracytoplasmic Sperm Injection (IVF/ICSI) with an antagonist protocol were evaluated. Patients were divided into three groups (n=53). Group 1 received 500 IU of hCG, group 2 received 1000 IU of hCG intrauterine injection before ET, and the control group underwent ET without hCG preceding intrauterine injection. RESULTS: There was no significant difference among the groups. The implantation rates were 18.86%, 13.52%, and 14.37%, chemical pregnancy rates were 34%, 32.1%, and 35.3%, and clinical pregnancy rates were 34%, 32.1%, and 31.4% respectively. CONCLUSION: The pregnancy outcome in IVF/ICSI /ET cycles cannot be improved through hCG intrauterine injections before ET.

A Comparison of the Effects of Transdermal Estradiol and Estradiol Valerate on Endometrial Receptivity in Frozen-thawed Embryo Transfer Cycles: A Randomized Clinical Trial.

BACKGROUND: The purpose of this study was to determine the optimal endometrial preparation protocol by comparing the clinical outcome of two methods of endometrial preparation in frozen-thawed embryo transfer (FET) cycles, including that is, oral estradiol and 17ß-estradiol transdermal patch. METHODS: In this randomized controlled trial, women underwent either conventional IVF or intracytoplasmic sperm injection (ICSI) who had at least two top-quality embryos appropriate for cryopreservation and frozen embryos from previous cycles. In the study group (n=45), 17-B estradiol transdermal patches 100 µg were applied from the second day of the cycle and continued every other day. Then, each patch was removed after four days. In the control group (n=45), oral estradiol valerate 6 mg was started at the same time and continued daily. RESULTS: There was a significant difference in estradiol level on the day of progesterone administration and the day of embryo transfer between the two groups (p= 0.001 in both), but no significant difference was observed between them in biochemical and clinical pregnancy rates (32.6% vs. 33.3%, p=1.000 and 30.2% vs. 33.3%, p=0.810, respectively). CONCLUSION: It is suggested that estradiol transdermal patches be used instead of oral estradiol in FET cycles. Due to the reduced costs, drug dose, and emotional stress as well as the simplicity of the protocol for patients.

Results from adding recombinant LH for assisted reproductive technology treatment: A randomized control trial.

BACKGROUND: Based on classical two-cell, two-gonadotropin theory, in the follicle, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) put on their main effects on the granulosa and theca cells. LH is essential for androgens production. Androgens are used for estradiol production by granulosa cells. Profound suppression of LH concentrations in some normogonadotropic patients can cause several adverse effects. OBJECTIVE: The main clinical purpose of this study was that normoresponder women treated with controlled ovarian super ovulation for IVF or ICSI may benefit from co-administration of rLH. MATERIALS AND METHODS: 40 patients who were candidates for assisted reproductive technology (ART) were randomly selected. In all patients long luteal protocol was used for ovulation induction. Patients were randomly divided into two groups: Group 1 (n=20) with standard long protocol (GnRH agonist) and r-FSH alone, Group 2 (n=20) with standard long protocol (GnRH agonist) and r-FSH with r-LH. RESULTS were statistically analyzed and compared in two groups. RESULTS: The number of retrieved oocytes, mature oocytes, cleaved embryos, transferred embryos, estradiol levels in Human chorionic gonadotropin (hCG) administration day, implantation rate and clinical pregnancy rate in group 2 were higher but not significantly different. CONCLUSION: Administration of rLH in late follicular phase had no beneficial effect on outcomes in young women with mean age of 31 years. Maybe a greater sample size should be used to see the effects more accurately; also it is possible that rLH will be useful in older patients. Registration ID in IRCT: IRCT201304302575N4.

Effect of oocyte activation with calcium ionophore on ICSI outcomes in teratospermia: A randomized clinical trial.

BACKGROUND: Chemical activation is the most frequently used method for artificial oocyte activation (AOA), results in high fertilization rate. OBJECTIVE: This prospective, randomized, unblinded, clinical study aimed to evaluate the efficiency of oocyte activation with calcium ionophore on fertilization and pregnancy rate after intracytoplasmic sperm injection (ICSI) in infertile men suffer from teratoospermia. MATERIALS AND METHODS: Thirty eight women with teratoospermic partner underwent ICSI with antagonist protocol. A total of 313 metaphase II (MII) oocytes were randomly divided into two groups: In the oocytes of the control group (n=145), routine ICSI was applied. Oocytes in the AOA group (n=168) immediately after ICSI, were entered in culture medium supplemented with 5 µΜ calcium ionophore (A23187) for 5 minutes and then washed at least five times with MOPS solution. In both groups, the fertilization was evaluated 16-18 hours after ICSI. RESULTS: The number of fertilized oocytes and embryos obtained were significantly different between two groups (p=0.04). There was no significant difference between the two studied groups regarding the fertilization and cleavage rate (95.33% vs. 84.4%, p=0.11; and 89.56% vs. 87.74%, p=0.76, respectively). Implantation rate was higher in AOA group than in control group, but the difference was not significant (17.64% vs. 7.4%, p=0.14). No significant differences were observed in chemical and clinical pregnancy rate between groups (47.1% vs. 16.7%, p=0.07; and 41.2% vs. 16.7%; p=0.14, respectively). CONCLUSION: We didn't find significant difference in the implantation, fertilization, cleavage and pregnancy rates between the two groups but could significantly increase the number of fertilized oocytes and embryos obtained. Finally oocyte activation with calcium ionophore may improve ICSI outcomes in infertile men suffer from teratoospermia. Further study with more cases can provide greater value.