Background : progesterone used as a therapeutic agent in human pregnancy. The sufficient evidence to hypothesize that progesterone may have teratogeniceffect on the reproductive system of female offspring. Objectives: This study was established to explore the individual impact of differ ent doses of progesterone during intrauterine period on reproductive system of female mouse, and on some reproductive parameters. Materials and Methods: ninety adult female mice (8-10 weeks) and weight (25-28) gm divided into three groups. Control group (G1) was treated daily (IM) injection with sesame seed oilfrom 1-14 day of pregnancy, and other two groups that treated with different doses of progesterone G2 (0.4mg/kg. B.wt/day), G3 (0.8mg/kg. B.wt/day), daily (IM) injection of progesterone from 1-14 day of pregnancy then selecting of Female offspring and sacrificed at age zero day, one month, two month. Parameter analysis involvedanogenital distance , body and ovary weights, , length of epithelial cells, number and diameter of follicles (Primordial , Primary , Secondary and Mature antral) , corpus luteum and using histological section by (motic image plus) and hormonal assay including proges terone and Estrogen. Results: The results of this study demonstrated that at one month, two months after birth, there was a highly significant increase P< 0.01 in theanogenital dis tance . The statistical analysisshowed no statistical significant difference in the body and ovary weights , at one month after birth, The statistical analysisshowed highly statistically significant decreased(P< 0.01 ) in both G2 and G3 in the number of follicles . At one,two months after birth, there was a highly significant decreased (P< 0.01 ) in both G2 and G3 in the number ofcorpora lutea. At age two month, there was a highly significant decreased (P< 0.01 ) in both G2 and G3 in the height of epithelial cell layer.There was a highly significant decreased (P< 0.01 ) in both G2 and G3 in the diameter of follicles (Primordial , Primary , Secondary and Mature antral) follicles . There was a highly significant decreased (P< 0.01 ) in both G2 and G3 in Estrogen and Progesterone levelof female off spring when compared with the control group G1. Conclusion: The results showed higher doses of progesterone for long period in pregnancy can impact some reproductive parameters of female offspring mice. Keywords : Progesterone, corpora lutea, Estrogen,anogenital distance
The association between the two hormones (progesterone and Activin A) in infertile women on the day of ova pick up and their relationship with pregnancy status in assisted reproductive programs are both poorly understood. To determine the correlation of progesterone and activin A on the day of ova pick up with pregnancy status of women undergoing IVF/ICSI cycle. The study was conducted on 80 infertile couples. The serum at day of ova pick up was collected. Serum progesterone and activin A analysis were done for all samples for activin A. Out of eighty infertile females twenty-five became pregnant (Pregnancy rate = 31%). Serum progesterone levels at days of oocytes pick up was significantly higher in pregnant females than non-pregnant (9.22 ± 0.54 vs. 4.47 ± 0.44; p < 0.001). There was a significantly higher serum activin levels at day of oocytes pick up in pregnant women compared to non-pregnant (2.19 ± 0.04 vs. 1.52 ± 0.04; p < 0.001). The cut-off value of serum progesterone at day of oocytes picks up was > 7.5 ng/ml and the cut-off value of serum activin A at day of oocytes pick up was > 1.85 ng/ml. Pregnant women had higher levels of the hormone progesterone and Activin A than non-pregnant women, which is significantly correlated. This result can be utilized to predicate the pregnancy status early in IVF Centers.
Background: Analysis of human reports and comparison with results of exper-imental animals indicate that the effects of progesterone on human not analo-gous to experimental animals fetus, many studies showed that exposure to pro-gesterone during developing of genital tract of human fetus was not teratogenic. Other studies which performed on laboratory animals found association between progesterone administration during gestation and genital malformation. Objectives: to explore the effect of progesterone in 10.2mg/kg intraperitoneal injection in mice on testis development and anogenital distance. Materials and Methods: ten pregnant mice divided into five mouse control group that injected10.2mg/kg sesame oil and treated group that injected proges-terone at dose 10.2mg/kg/day allover gestation to the seventh day postnatally, mice offspring sacrificed, the anogenital distance, weight and diameter of testis were measured ,histological slides were prepared and examined for histopatho-logical change and measurement of seminiferous tubules diameter, germinal epithelium thickness and interstitial space were done . Results: the current study found anogenital distance decrement and histopatho-logical changes in mice offspring testis as hemorrhage or congestion of blood vessels ,irregular shapes of seminiferous tubules with atrophy, detachment of spermatogenic cells from basement membrane, death of spermatogenic cells and destruction of Sertoli and leydig cells ,it is also showed wider interstitial tissue and thinner germinal epithelium. Conclusions: The present study indicate study that progesterone injected in mice at dose 10.2 mg/kg /day (the equivalent human dose allover gestation was em-bryotoxic and teratogenic, it may cause feminization of male offsprings repre-sented by decrement the anogenital distance in mice and hypospadias in human .
The 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme is a key methionine and folate metabolism enzyme that is found in oocytes and embryos in preimplantation stages and plays a vital role in female reproduction.To assess the impact of MTHFR genetic polymorphisms (C677T and A1298C) on follicular stimulating hormone (FSH), luteinizing hormone(LH), Estradiol (E2), progesterone and antimullerian hormone (AMH) in female receiving intracytoplasmic sperm injection (ICSI), 85 infertile women undergoing ICSI treatment at the High Institute of Infertility Diagnosis and Assisted Reproductive Technologies in Baghdad, Iraq, were recruited. These patients had their MTHFR polymorphism genotypes examined, FSH, LH, E2, progesterone, and AMH levels were compared between groups. Furthermore, all demographic characteristics as well as ICSI outcomes were compared between pregnant and non-pregnant women. The research revealed no discernible variation between the means of FSH, LH, E2 and AMH with respect to the 219A>C(rs1801131) (A1298C) genotypes (p > 0.05). Progesterone level was significantly differed with high level found in CC followed by AA and AC. There was no statistically significant variation in hormonal features between CC, CT, and TT for A1298C, 219A>C(rs1801133). The demographic features (age, duration, type of infertility, cause of infertility and previous trial) were not notably different between women who were pregnant and those who were not. In women undergoing ICSI, the maternal MTHFR polymorphisms is not related to FSH, LH, E2 and AMH. MTHFR polymorphisms therefore don't offer useful information regarding the hormonal levels in our groups.
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.
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.
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.
Receptive endometrium is essential for successful embryo implantation and is created by the synergistic activities of estrogen and progesterone, as well as support from other endocrine, paracrine, and autocrine pathways. Granulocyte Colony Stimulating Factor (G-CSF) may play a crucial role in modulating the immune response to enhance implantation. To estimate the role of granulocyte-colony stimulating factor on the clinical intracytoplasmic sperm injection (ICSI) outcome parameters. A prospective comparative study with random sample selection was carried out from 2021 to 2023 at the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies, Al-Nahrain University. It included 80 women with infertility, with or without previous failure trials of intracytoplasmic sperm injection, who completed IVF and ICSI protocols and reached the day of embryo transfer. On the day of embryo transfer, patients were divided into two groups: 49 patients received no additional treatment (group 1), and 31 patients received granulocyte-colony stimulating factor subcutaneous injection within one hour of embryo transfer (group 2). The implantation rate was 13.3% in group 2 compared to 7.6% in group 1. The chemical and clinical pregnancy rates were 29.0% and 25.8% in group 2, while group 1 had 18.4% for both chemical and clinical pregnancy rates. The pregnancy and implantation rates were slightly higher in group 2, but the difference was not significant. More research is needed to support the use of G-CSF as a standard treatment in ICSI patients.
Female infertility is caused by ovulation issues, tubal disorders, uterine abnormalities, endometriosis, and peritoneal factors. For years, intrauterine insemination has been used to treat infertility alone or with ovarian stimulation. Obtaining adhesion ligands and losing inhibitory components are necessary for pregnancy. LIF promotes and differentiates proliferation and differentiation in embryonic, hematopoietic, and endothelial cells. LIF also controls prostaglandins (PGs), which mediate implantation and decidualization. The measuring hormone profile on cycle day 2 before control ovarian stimulation including FSH, LH, E2, Prolactin, TSH, and AMH. Serum LH, E2. The progesterone level was estimated on the day of triggering. The effect of LIF gene genotypes on hormone level. The hormone levels of 100 intrauterine inseminated women were measured on the second day of the cycle and the day of ovulation. DNA extraction for LIF gene variation detection utilizing sequencing and HRM. The current study found no significant differences between pregnant and non-pregnant groups for hormone levels, genotype, and genetic effect on female hormone levels with (P ≥0.05). The LIF gene did not affect hormone levels in infertile females may be due to the tiny samples or the complex signaling chain that happens during implantation.
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.
In present study, it was investigated the effect of clomiphene citrate on the ovaries reproductive hormones and embryos of mature female mice, were studied. Female mice treated with (5, 10,50 mg/kg ) daily for 7 days. Results cleared that cross section showed a significant increase (p<0.05) in multi follicular (different numbers )on the right and left ovaries of female mice. In other hand; there were a significant elevation (p<0.05) in the follicle stimulation hormone(FSH), estrogens and progesterone concentration, while, no significant changes were noticed in luteinizing (LH). Conclusions: Clomiphene citrate is the best initial treatment especially in relevance with ovulatory problems (dysfunction), and has a super stimulatory effect on ovulation, thereby increasing the number of recruited follicles in albino female mice rather than affecting the follicular steroidogenic function, and its induce multi follicle ovum forming. Similarly, it has positive affection on gonadotropene hormones, eventually it leads to a twin pregnancy. Combined c with appropriately timed IUI, Clomiphene citrate treatment also increases cycle fecundity in couples with unexplained infertility.
Inhibition of luteinizing hormone (LH) by gonadotropin releasing hormone (GnRH) antagonist may lead to suboptimal response during ovarian stimulation. In addition, several studies suggest that low level of LH is associated with lowered fertilization and implantation rate and increased early pregnancy loss rate. The aim of this study is to study the effect of adding low dose human chorionic gonadotropin (hCG - 200 IU), as an LH supplement, to recombinant follicle stimulating hormone (rFSH) in a GnRH antagonist cycles in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Sixty-three infertile women undergoing IVF were randomly divided into two groups. One group was stimulated with the conventional stimulation protocol (rFSH alone), while the second group received 200 IU hCG in addition to rFSH in the late follicular phase (hCG + rFSH). Both groups' results including pregnancy rate, total dose of rFSH required, duration of stimulation, endometrial thickness, oocytes and embryos characteristic, serum hormone levels (Testosterone, Estradiol, Progesterone, and LH) and level of epidermal growth factor (EGF) were compared. The results show that pregnancy rate among the group of women who received the low dose hCG was higher than those who did not receive hCG. However, this difference did not reach statistical significance. Furthermore, other cycle outcomes and hormonal values were comparable between the two stimulation protocols.
Human chorionic gonadotropin is a glycoprotein hormone produced by the placenta. It exists in several isoforms with long half-lives (hours) and angiogenic potential; it maintains the corpus luteum to produce progesterone. This study aimed to evaluate Human chorionic gonadotropin concentration in follicular fluid and its effect on oocyte maturity and pregnancy rate, and whether it can be used as a noninvasive biomarker for predicting oocyte competence and pregnancy rate during intracytoplasmic sperm injection cycles. Infertile women undergoing ICSI treatment were included in the study. An antagonist protocol was used for ovulation induction. Patients were divided into two groups: pregnant women (n=18) and non-pregnant women (n=22). Samples of follicular fluid were collected on the day of oocyte pick-up. Chemiluminescent Immunoassay (CLIA) equipment was used for the quantitative determination of total β-human chorionic gonadotropin in follicular fluid. The mean beta-human chorionic gonadotropin level showed a highly significant increase relative to the mean level of non-pregnant women (110.24 ±20.50) versus (56.195 ±29.45). Moreover, there was no significant relationship between the levels of beta-human chorionic gonadotropin follicular fluid and the total number of oocytes and oocyte quality in the two groups. The Beta Human chorionic gonadotropin concentration in the follicular fluid plays an important and influential role in the prediction of pregnancy rates. Despite this, follicular fluid hCG level showed no relationship with the total number and quality of oocytes in the pregnant and non-pregnant groups.
Background: The effects of taking oral contraceptive pills that contain steroid hormones (estrogen and progesterone) during pregnancy on some aspects of fetus and newborn have been previously reviewed. Objectives: The objectives of this study are to detect the effect of using different doses of progestin and estrogen (contraceptive pills OCPs) by pregnant female mice on the gonadal development of their male fetuses, and on their pregnancy outcome. Materials and Methods: Ninety female mice were divided equally into three major groups: two experimental (G1 and G2) and control group according to the level of the dose. Administration of OCPs (either 0.034 or 0.068 mg/kg b. wt. /d dissolved with 0.1ml distilled water) orally once a day, were started at the first day of gestation and continued till day 14 for the experimental groups G1 and G2 respectively. When the female in each experimental and control groups reach day 17 of gestation, 15 animals of each group were sacrificed, whereas the other 15 animals were left to be sacrificed at birth time. Weight and numbers of fetuses were recorded, in addition, histological study for their testes were done. Results: The statistical analysis showed a highly significant (P<0.01) decrease in weights and numbers of fetuses (males and females), and highly significant decrease ( (P<0.01) in the testes diameter of fetuses belonged to mothers treated with normal and double dose of OCPs at day 17 and at birth time. In addition, fetuses belongs to G2 mothers revealed testicular undescending to its normal position and remained adjacent to the kidneys at the upper part of the abdominal cavity in comparison with control group. Conclusion: Administration of steroid hormones orally to pregnant female mice for 14 days causes a highly significant decrease in the weight and number of fetuses at day 17 and at birth time and cause negative effect on the diameter of the fetal testes. The OCPs can inhibit at its high dose, the descending of the testes to its normal location at the pelvic cavity and then to the inguinal canal.
Human chorionic gonadotropin is a glycoprotein hormone produced by the placenta. It exists in several isoforms with long half-lives (hours) and angiogenic potential; it maintains the corpus luteum to produce progesterone. This study aimed to evaluate Human chorionic gonadotropin concentration in follicular fluid and its effect on oocyte maturity and pregnancy rate, and whether it can be used as a noninvasive biomarker for predicting oocyte competence and pregnancy rate during intracytoplasmic sperm injection cycles. Infertile women undergoing ICSI treatment were included in the study. An antagonist protocol was used for ovulation induction. Patients were divided into two groups: pregnant women (n=18) and non-pregnant women (n=22). Samples of follicular fluid were collected on the day of oocyte pick-up. Chemiluminescent Immunoassay (CLIA) equipment was used for the quantitative determination of total β-human chorionic gonadotropin in follicular fluid. The mean beta-human chorionic gonadotropin level showed a highly significant increase relative to the mean level of non-pregnant women (110.24 ±20.50) versus (56.195 ±29.45). Moreover, there was no significant relationship between the levels of beta-human chorionic gonadotropin follicular fluid and the total number of oocytes and oocyte quality in the two groups. The Beta Human chorionic gonadotropin concentration in the follicular fluid plays an important and influential role in the prediction of pregnancy rates. Despite this, follicular fluid hCG level showed no relationship with the total number and quality of oocytes in the pregnant and non-pregnant groups.