HOX cluster and their cofactors showed an altered expression pattern in eutopic and ectopic endometriosis tissues.

Endometriosis is major gynecological disease that affects over 10% of women worldwide and 30%-50% of these women have pelvic pain, abnormal uterine bleeding and infertility. The cause of endometriosis is unknown and there is no definite cure mainly because of our limited knowledge about its pathophysiology at the cellular and molecular levels. Therefore, demystifying the molecular mechanisms that underlie endometriosis is essential to develop advanced therapies for this disease. In this regard, HOX genes are remarkable because of their critical role in endometrial development and receptivity during implantation, which is attributed to their ability to mediate some of the sex steroid functions during the reproductive period. Access to the expression profiles of these genes would provide the necessary information to uncover new genes for endometriosis and assist with disease diagnosis and treatment. In this study we demonstrate an altered expression pattern for the HOX clusters (A-D) and their cofactors in both eutopic and ectopic conditions compared to control tissue biopsies. Remarkably, most of the intensive changes occurred in eutopic samples from endometriosis patients compared to control tissue biopsies. Pathway analysis revealed the involvement of differentially expressed genes in cancer that correlate with an association between endometriosis and cancer. Our results suggest critical roles for the HOX cluster and their cofactors in endometriosis pathophysiology.

Association between early embryo morphokinetics plus cumulus cell gene expression and assisted reproduction outcomes in polycystic ovary syndrome women.

RESEARCH QUESTION: Can a combination of time-lapse morphokinetic parameters and cumulus cell gene expression in polycystic ovary syndrome (PCOS) women be used to predict assisted reproductive treatment outcome? DESIGN: A total of 547 embryos from 100 intracytoplasmic sperm injection (ICSI) cycles were evaluated. Fifty women with PCOS and 50 women who were categorized as tubal factor infertility were recruited. Time-lapse records were annotated for time to pronuclear fading (tPNf), time to 2 to 8 cells (t2-t8), reverse cleavage, direct cleavage and also for the presence of multinucleation. Expression levels of three genes involved in mitotic divisions, diaphanous-related formin 2 (DIAPH2), nibrin (NBN) and NIMA-related protein kinase (NEK4), were measured in 100 associated cumulus cell samples using quantitative real-time polymerase chain reaction. RESULTS: Expression of DIAPH2 and NBN was significantly higher in the embryos of PCOS patients that resulted in implantation, biochemical and clinical pregnancies as well as live birth compared with embryos that were negative for these outcomes (P <0.01). However, in the tubal factor group, NBN gene expression was significantly higher in embryos resulting in biochemical pregnancy, clinical pregnancy and live birth (P <0.01) only. Multivariate logistic regression analysis showed that tPNf together with DIAPH2 gene expression were independent prognostic factors of clinical pregnancy rate and live birth in both groups. CONCLUSIONS: Some time-lapse embryo parameters may be related to cumulus gene expression and clinical outcome. Furthermore, the expressions of cumulus cell genes involved in mitotic divisions are significantly associated with ICSI outcome using Day 3 embryo transfer.

Assessing ICSI outcome by combining non-invasive indicators: Early time-lapse morphokinetics and apoptosis in associated cumulus cells among women with the polycystic ovarian syndrome.

Cumulus cells features and embryo developmental events can be considered as noninvasive indicators for embryo selection and clinical outcomes. A combination of time-lapse morphokinetic parameters and cumulus cell apoptosis in women with polycystic ovarian syndrome (PCOS) was evaluated for predicting pregnancy outcome. We assessed a total of 547 embryos from 100 intracytoplasmic sperm injection (ICSI) cycles. Time-lapse records were interpreted in time to pronuclear fading (tPNf), time to 2 to 8 cells (t2-t8), direct cleavage, reverse cleavage, and also for the presence of multinucleation. Percentages of apoptosis were identified in 100 associated cumulus cell samples using the TDT-mediated dUTP-biotin nick end-labeling assay. The significant decrease of apoptotic cumulus cells was detected in patients with chemical and clinical pregnancies as well as live birth among patients PCOS and in the tubal infertility group (p > 0.05). Furthermore, significantly higher implantation rate and also significantly lower cases of early pregnancy loss were observed in the group of oocytes with less apoptotic cumulus cells. Multivariate logistic regression analysis showed that tPNf together with cumulus cell apoptosis were independent prognostic factors of chemical pregnancy, clinical pregnancy rate, and live birth. Time-lapse embryo parameters may not reflect the cumulus cell apoptosis rate. However, the rate of apoptotic cumulus cells is significantly associated with ICSI outcome using Day 3 embryo transfer.

Noninvasive assays of in vitro matured human oocytes showed insignificant correlation with fertilization and embryo development.

PURPOSE: Recently, the upgrading of in vitro maturation (IVM) of human oocytes as a promising strategy has emerged in assisted reproductive technology (ART). The goal was to evaluate the correlation of the in vitro matured oocytes selected on the basis of the zona pellucida (ZP) birefringence and meiotic spindles (MS) detection with fertilization and subsequent embryo development in ICSI program. METHODS: A total of 168 immature oocytes [germinal vesicle (n = 140) and metaphase I (n = 28)] obtained from patients undergoing oocytes retrieval for ICSI. After in vitro culture for 24-40 h, 112 (67 %) oocytes reached to MII stage. Using a polarized microscopy, the presence of MS and ZP birefringence were assessed in matured oocytes, followed by ICSI performance. RESULTS: The rates of fertilization in oocytes with spindles (51.3 %) were similar to that of the oocytes without spindles (50.7 %; P = 1.00). Moreover, the fertilization rates in high birefringence (HB) oocytes was not statistically different than oocytes with low birefringence (LB) (P = 0.44). The findings also showed that 64.9 % of the fertilized oocytes developed to embryos, in which 33.3 % were derived from spindle-detected oocytes. Regarding the ZP birefringence, 35.5 % of the embryos were derived from HB oocytes. CONCLUSIONS: There were insignificant relationships between the MS detection and ZP birefringence score with the rates of fertilization and embryo development in IVM oocytes.

Association of IL-17A and IL-17 F gene polymorphisms with recurrent pregnancy loss in Iranian women.

PURPOSE: Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more miscarriages before the 20th week of pregnancy. T helper17 cells are a novel subset of T cells, which secrete IL (Interleukin)-17 and are known to be involved in inflammation, autoimmunity and rejection of non-self tissues. Herein, we studied the association between IL-17A rs2275913 and IL-17F rs763780 gene polymorphisms with RPL in Iranian women. METHODS: A case-controlled study was performed on two groups consisting of 85 healthy women with at least one delivery and 85 women with the history of two or more RPLs. The frequency of IL-17A rs2275913 and IL-17 F rs763780 polymorphisms were determined by PCR-RFLP. RESULTS: In the RPL group, the genotypes frequencies of rs2275913 polymorphism were GG (8.2 %), AG (30.6 %), and AA (61.2 %) and in the control group, were GG (3.5 %), AG (42.4 %) and AA (54.1 %). Statistical analysis showed no significant difference between the genotypes of AA, AG and GG in the two groups (p = 0.1). The genotypes frequencies of rs763780 polymorphism were TT (43.5 %), TC (49.4 %) and CC (7.1 %) in the RPL group; whereas the frequencies were TT (25.9 %), TC (70.6 %) and CC (3.5 %) in the control group. Statistical analysis revealed a significant difference in the TT, TC, and CC genotypes frequencies between the case and the control groups (p = 0.01). CONCLUSIONS: Our findings indicate that IL-17F polymorphism, rs763780, might be associated with a high risk of RPL in Iranian women.

A comparison of pregnancy rate before and after the administration of HCG in intrauterine insemination.

PURPOSE: Intrauterine insemination (IUI) is one of the first treatments of infertility. In natural cycles, women conceive when an intercourse takes place during a 6-day period ending on the day of ovulation. The current practice in IUI cycles is to perform IUI 24-36 h after the HCG administration, when the ovulation already took place. In this study, HCG was administered after IUI, which more closely resembles the fertilization process in natural cycles. The aim of the present study is to compare the fertility rates in an IUI protocol in women who took an HCG injection before and after the IUI. METHODS: This study was conducted on 100 infertile couples who referred to the infertility research center of Shahid Sadoughi University of Medical Sciences. They were divided into two groups: HCG injection before IUI and HCG injection after IUI. The main outcome measure was the result of a ß HCG test that was done two weeks after the IUI; if it was positive, transvaginal sonography would be performed in the seventh week for clinical confirmation of pregnancy. RESULTS: The analysis included 50 cycles with HCG administered before and 50 cycles with HCG administered after the IUI. The pregnancy rates were 10 and 12 % (P = 0.85), respectively. Independent factor affected the cycle outcome was the time of infertility. CONCLUSION: HCG administration after IUI brought about no improvement in the pregnancy rate. Therefore, HCG can be administered either before or after IUI.

The association of higher thyroid stimulating hormone levels in the normal range with unexplained infertility: A cross-sectional study.

Background: Since thyroid hormones have an essential role in energy production, early development of the human placenta, embryo development, and implantation, abnormalities in thyroid function can significantly affect pregnancy outcomes. Objective: The present study aimed to investigate the effect of higher thyroid-stimulating hormone (TSH) levels in the normal range in euthyroid women with unexplained infertility. Materials and Methods: In this cross-sectional study, we evaluated the data for 300 euthyroid women aged between 18 and 39 yr with normal TSH levels ( ≤ 5 mIU/L) referred to Yazd Reproductive Sciences Institute, Yazd, Iran from December 2018-March 2021 in 2 groups: the case group (with unexplained infertility) and the control group (with male factor infertility). Finally, age, body mass index, and serum levels of TSH were extracted from participants' medical records and compared between groups. Results: The mean age and TSH level of participants were 31.52 ± 3.52 yr and 1.24 ± 2.59 mIU/L, respectively. 142 women (47.3%) had TSH < 2.5, and 158 women (52.7%) had TSH ≥ 2.5 mIU/L. The women with unexplained infertility had significantly higher TSH levels than controls in the same normal range (0.62 vs. 0.64 mIU/L, p < 0.001). Although a more significant proportion of women in the case group had TSH levels > 2.5 mIU/L, we did not find a significant association between TSH levels and age or body mass index. Conclusion: Women with unexplained infertility have a higher level of serum TSH in the normal range ( ≥ 2.5 mIU/L) than the control group. So, the effect of TSH treatment on these women should be considered.

Adjuvant growth hormone therapy in antagonist protocol in poor responders undergoing assisted reproductive technology.

PURPOSE: The incidence of poor ovarian response in controlled ovarian stimulation (COH) has been reported in 9-24 % of IVF-ET cycles. Growth hormone augments the effect of gonadotropin on granulosa and theca cells, and plays an essential role in ovarian function, including follicular development, estrogen synthesis and oocyte maturation. The aim of this study was to assess IVF-ET cycle outcome after the addition of growth hormone in antagonist protocol in poor responders. MATERIALS AND METHODS: Eighty-two poor responder patients selected for ART enrolled the study and were randomly divided into two groups. Group I (GH/HMG/GnRHant group, n = 40) received growth hormone/gonadotropin/GnRH antagonist protocol and group II (HMG/GnRHant group, n = 42) received gonadotropin/GnRH antagonist protocol. RESULTS: The number of retrieved oocytes was significantly higher in GH/HMG/GnRHant group than HMG/GnRHant group, 6.10 ± 2.90 vs. 4.80 ± 2.40 (p = 0.035) and the number of obtained embryos was also significantly higher in GH/HMG/GnRHant group than HMG/GnRHant group, 3.7 ± 2.89 as compared to 2.7 ± 1.29 (p = 0.018). There were no significant differences between groups regarding implantation, and chemical and clinical pregnancy rates. CONCLUSION: Our study showed that co-treatment with growth hormone in antagonist protocol in patients with a history of poor response in previous IVF-ET cycles did not increase pregnancy rates.

Effect of dietary approaches to stop hypertension, and standard diets with and without curcumin on interleukin-1 alpha, 5-alpha reductase gene expressions, and androgenic and glycemic profile in polycystic ovary syndrome women undergoing in vitro fertilization treatment: A study protocol.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases with major reproductive and metabolic complications with an impact on public health. Hyperandrogenism and chronic inflammation have been suggested as the leading cause of pathophysiology and clinical manifestations associated with PCOS. It seems that the altered expression of genes involved in the synthesis of pro-inflammatory cytokine and androgens contribute to the promotion of PCOS. Objective: This trial aims to determine the effects of dietary approaches to stop hypertension (DASH) and standard diets with and without curcumin supplementation on the gene expression of interleukin -1 alpha(IL1α), 5α reductase and androgenic and glycemic profile among PCOS patients, who are candidates for in vitro fertilization. Materials and Methods: 96 infertile women with PCOS, aged 18-40 yr, will participate in this randomized, placebo-controlled clinical trial. Based on treatment conditions and body mass index, the participants will be randomly divided into 4 equal groups using a randomized block design. They will receive a DASH or standard diet containing 52% carbohydrate, 18% protein, and 30% total fat, with the same prescribed sodium, plus 500 mg twice daily curcumin or placebo for 12 wk. The mRNA expression of IL-1α, 5α reductase, and androgenic and glycemic profiles will be measured at baseline and at the end of the study. Conclusion: Concomitant administration of DASH diet and curcumin supplementation may reduce IL-1α, 5α reductase gene expressions, and improve glycemic and androgenic profiles.

Efficacy of low-dose hCG in late follicular phase in controlled ovarian stimulation using GnRH agonist protocol.

OBJECTIVE: Safe, simple and cost-effective protocol is an important goal in ART cycles. The aim of this prospective study was whether administration of low-dose hCG in late follicular phase can be used clinically to replace gonadotropin administration in GnRH long protocol. MATERIALS AND METHODS: 122 patients who were candidates for ART enrolled the study and randomly divided into two groups. The control group (n = 62) received standard long protocol and gonadotropin administration continued until the day of hCG injection (10,000 IU) for final follicular maturation. The study group (n = 60) received GnRH long protocol and when at least ≥6 follicles with mean diameter ≥12 mm were observed in both ovaries, hMG was displaced by 200 IU per day of hCG until final follicular maturation. RESULTS: There were no significant differences in age, basal FSH, infertility duration and infertility etiology between two groups. There were no statistically significant differences between two groups regarding chemical pregnancy, clinical pregnancy, ongoing pregnancy, and abortion per cycle (50, 40, 40, and 20 % in study group vs. 45.2, 35.5, 35.5, and 21.4 % in control group, respectively). Mean dose of used gonadotropins was significantly higher in control group than that in the study group (2,524 ± 893 IU in control group and 1,439 ± 433 IU in study group) (p = 0.000). CONCLUSION: According to our data, we recommend the use of low-dose hCG in GnRH long protocol because of lower doses of used gonadotropins.

Transfer of blastocysts derived from frozen-thawed cleavage stage embryos improved ongoing pregnancy.

PURPOSE: The aim of our study was to compare the transfer of embryos that are cryopreserved in cleavage stage after thawing with the transfer of embryos after thawing and culture in sequential media until blastocyst formation. METHODS: In this prospective clinical study, we have evaluated 134 cycles of ART treatment for infertility. Frozen embryos were thawed and then cultured in sequential media until blastocyst stage in blastocyst group and were compared with thawed embryos in cleavage stage group. RESULTS: Implantation rate was significantly higher in blastocyst group (30 %) compared to cleavage group (17 %). No statistical differences were reported in chemical and clinical pregnancy rates between groups. Ongoing pregnancy rate was significantly higher in blastocyst group compared to cleavage group (42.9 vs. 24.6 %). CONCLUSIONS: Our results indicated that blastocyst formation after thawing of cleavage stage embryos is a good predictor for embryo viability and pregnancy outcome.

Correction to "Effect of vitamin D insufficiency treatment on fertility outcomes in frozen-thawed embryo transfer cycles: A randomized clinical trial" [Iran J Reprod Med 2014; 12: 595-600].

[This corrects the article on p. 595 in vol. 12 PMCPMC4248143.].

The effect of misoprostol on the removal of endometrial polyps: A pilot clinical trial.

Background: Endometrial polyps are one of the most common gynecological disorders with a high frequency among infertile women. Hysteroscopic polypectomy remains the gold standard for the treatment of endometrial polyps. As alternative treatments, few drugs have been evaluated to date. Objective: To investigate the possible effect of misoprostol on the elimination of endometrial polyps. Materials and Methods: In this clinical trial we examined 30 infertile women whose endometrial polyps were confirmed by transvaginal ultrasound with saline injection. All women were administered 400 mg of misoprostol: 200 mg orally and 200 vaginally. 8 hr later, sonography with saline injection was performed again and all women were examined for the presence or absence of endometrial polyps. Finally, the diagnosis was confirmed for all women using hysteroscopy. The main outcome of this study was the elimination of endometrial polyps after misoprostol administration. Results: The average size of the endometrial polyps was 14.33 ± 4.26 mm, with a range of 7-22 mm. After misoprostol administration, in 12 out of the 30 women who had shown endometrial polyps in the initial examination, no polyp was found. At follow-up it was found that the smallest endometrial polyp that had been eliminated was 8 mm and the largest was 22 mm. Conclusion: The findings of our study revealed that misoprostol can remove up to 40% of endometrial polyps. This drug has the potential to be used as a safe and low-cost first-line treatment before performing hysteroscopic polypectomy.

Corrigendum to "The effect of misoprostol on the removal of endometrial polyps: A pilot clinical trial" [Int J Reprod BioMed 2022; 20: 461-468].

[This corrects the article DOI: 10.18502/ijrm.v20i6.11441.].

Corrigendum to "Efficacy of 17 α- hydroxy progestrone on decreasing preterm labor in ART pregnancies: A randomized clinical trial" [Iran J Reprod Med 2013; 11: 785-790].

[This corrects the article on p. 785 in vol. 11 PMCPMC3941339.].

Correction to "Does the repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome improve in vitro fertilization cycles outcome? A clinical trial study" [Int J Reprod BioMed 2020; 18: 485-490].

[This corrects the article on p. 485 in vol. 18 PMCPMC7385917.].

Embryo selection in IVF.

To optimize success rates of IVF, selection of the most viable embryo(s) for transfer has always been essential, as embryos that are cryopreserved are thought to have a reduced chance of implanting after thawing. Recent developments challenge this concept. Evidence is accumulating that all embryos can now be cryopreserved and transferred in subsequent cycles without impairing pregnancy rates or maybe even with an improvement in pregnancy rates. In such a scenario no selection method will ever lead to improved live birth rates, as, by definition, the live birth rate per stimulated IVF cycle can never be improved when all embryos are serially transferred. In fact, selection could then only lower the live birth rate after IVF. The only parameter that could possibly be improved by embryo selection would be time to pregnancy, if embryos with the highest implantation potential are transferred first.

The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study.

PURPOSE: Comparing the effects of metformin or orlistat on hormone, lipid profile and ovulation status in obese women with polycystic ovary syndrome. METHODS: A total of 80 women were prospectively recruited to receive either metformin (n = 40) or orlistat (n = 40). Weight, BMI, waist, serum LH, total serum testosterone and lipid profile were assessed at baseline and after 3 months. The subjects' ovulatory status was assessed after 3 months. RESULTS: There was no significant difference in ovulation between the two treatment groups (30% vs 15%). Treatment with either drug showed a significant decline in body weight, BMI (Body Mass Index), and waist circumference, but the degree of decline in both groups was the same. Patients who were treated with orlistat, showed a significant reduction in total testosterone and serum lipid. Women in metformin group showed a significant reduction in serum LH. CONCLUSIONS: Both metformin and orlistat showed a similar effect on weight loss and ovulation rates.

Subcutaneous progesterone versus vaginal progesterone for luteal-phase support in frozen-thawed embryo transfer: A cross-sectional study.

BACKGROUND: Luteal-phase support is a complex and controversial issue in the field of reproductive management. OBJECTIVE: To compare the safety and efficacy of low-dose subcutaneous progesterone with the vaginal progesterone for luteal-phase support in patients undergoing rozen-thawed embryo transfer. MATERIALS AND METHODS: In this cross-sectional study, information related to 77 women that had frozen-thawed embryo transfer was reviewed. The patients were divided into two groups based on the route of progesterone administration used as a luteal-phase support. When the endometrial thickness reached ≥ 8 mm, in one group progesterone (Prolutex) 25 mg/ daily subcutaneous and in another group, vaginal progesterone (CyclogestⓇ) 400 mg twice or (EndometrinⓇ) 100 mg thrice daily, were administrated and continued until menstruation or in case of clinical pregnancy for 8 wk after the embryo transfer when the fetal heart activity was detected by ultrasonography. RESULTS: The patient's characteristics were matched and there was no significant difference. The chemical and clinical pregnancy rate was higher in the vaginal progesterone group compared to the prolutex group, but statistically unnoticeable, (40% vs. 29.6%, p = 0.367) and (28% vs. 22.2%, p = 0.581), respectively. CONCLUSION: The findings of this study demonstrate that the new subcutaneous progesterone can be a good alternative for intramuscular progesterone in women that dislike and do not accept vaginal formulations as luteal-phase support in assisted reproductive technology.

Correction to "The effect of endometrial injury on pregnancy rate in frozen-thawed embryo transfer: A randomized control trial" [Int J Reprod BioMed 2016; 14: 453-458].

[This corrects the article on p. 453 in vol. 14 PMCPMC4971562.].