The selection of protocols in controlled ovarian stimulation during intracytoplasmic sperm injection affect the treatment outcomes. Both GnRH agonist and GnRH antagonist protocols are clinically utilized, therefore comparision of these protocols is important for the evaluation of their laboratory and clinical outcomes.To compares the short GnRH agonist and GnRH antagonist protocols effectiveness in expected normal responder females undergoing intracytoplasmic sperm injection (ICSI). Methods: A retrospective study was involved 60 women aged less than 35 with antimullerian hormone (AMH) more than 2.5 ng/ml. Participants women were assigned to either group1 short GnRH agonist protocol and group2 GnRH antagonist protocol. The outcomes measured including total oocyte, mature and immature oocytes, number and quality of embryo and pregnancy rate.The short GnRH agonist protocol group showed statistical significant benefit in oocyte yield (p- value 0.04), metaphase I (p- value 0.09), metaphase II (p- value 0.03), embryo number (p- value 0.04), embryo quality (p-value 0.01) and pregnancy rate in expected normal responder women compared to GnRHantagonist protocol. The short GnRHagonist protocol reveals favorable ICSI outcomes than antagonist protocol and may be better choice in expected normal responder women.
Gonadotropin-releasing hormone antagonists are one of the GnRH analogs that were used in assisted reproductive technologies to produce prompt downregulation of pituitary gonadotropin secretion. During conventional antagonist protocol (CAP), exposure to high LH and E 2 occur that have the potential to worse clinical reproductive results. So the downregulation of pituitary secretion for short period during early follicular phase will result in synchrony in follicular developments and this will improve mature oocytes and total embryos numbers. 44 women as normal responders undergoing ICSI-ET cycles were randomized into two groups. The conventional group (CG) (n 30), gonadotropin started from menstrual cycle day 2 or 3 and continue until hCG trigger day, flexible protocol in which GnRH antagonists administered with follicular size (13-14 mm). In the sandwich group (SG) (n 14), a GnRH antagonist was administered for three days in which GnRH antagonists administered with follicular size (13-14 mm). Gonadotropin started from menstrual cycle day 3 and continue until hCG trigger day. Retrieved and MII oocyte mean numbers were significantly higher in SG than in CG ( P = 0.006, and 0.025), respectively. Embryos and frozen embryos mean total numbers were significantly higher in SG than in CG ( P = 0.004). SG patients have a higher pregnancy rate of 9/14 (64.3 %) than CG 12/30 (40.0 %) although not significant ( P =0.057). Early and short GnRH antagonists proved improvements in synchronization of follicular development, retrieved mature oocytes numbers, total embryos, frozen embryos, and pregnancy rates.
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.
To explore whether dual triggering for final oocyte maturation using a low dose of recombinant human chorionic gonadotropin (hCG) plus gonadotropin-releasing hormone agonist (GnRH-a) is as effective as the standard dose of recombinant hCG triggering alone in term of a total number of retrieved oocytes, fertilization and pregnancy rate in fresh autologous antagonist intracytoplasmic sperm injection (ICSI) cycles. 80 infertile women undergoing ICSI, aged ˂ 40 years, 18˂ Body mass index ˂30 Kg/m2 included in fresh autologous antagonist ICSI cycles. 40 women received a Standard dose of recombinant hCG (500 µg) alone and 40 women received GnRH-a (0.2 mg triptorelin plus 250 µg recombinant hCG) were used for final oocytes maturation. This study was conducted at the High Institute for Infertility Diagnosis and Assisted Reproductive Techniques, Al Nahrain University. The mean total number of retrieved oocytes, fertilization, and pregnancy rate were measured. The mean total oocyte number being statistically higher in the dual trigger group. The mean number of fertilized oocytes and clinical pregnancy rates was higher in the dual trigger group than in the control group, but the difference showed borderline statistical significance. Furthermore, fertilization rates show no statistical difference between the control group and the dual trigger group. Results of the study confirm that dual triggers show favorable improvement in fresh autologous antagonist ICSI cycles with the use of GnRH agonists plus hCG compared with hCG alone for triggering of final oocyte maturation.
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.
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.
Luteinizing hormone (LH) plays vital role for optimal follicular growth, maturation and is responsible for inducing ovulation, various protocols in ICSI cycles used to prevent the premature surge of luteinizing hormone. Currently, flexible GnRH antagonist protocols appears to be mostly used protocols. individualization of controlled ovarian hyper stimulation (COS) needs better timing of antagonist administration, assessing variation in LH levels during COS helps in determining appropriate initiation of inhibition .This prospective comparative observational analysis was made on one hundred twenty females with infertility who were undergoing ICSI flexible antagonist protocol at the “High Institute for Infertility Diagnosis and Assisted Reproductive Technologies/Al-Nahrain University” from October 2020 to April 2022, primary infertility was the with higher percentage (78.3%) than the secondary type. However; the main cause of infertility among the participant was male type (36.7%) fallowed by the combined one (20.8%). A highly significant difference was present in LH levels at all time points, with level decreasing from 4.99 ± 1.90 at baseline to 4.82± 2.15 at antagonist starting day to 1.63± 0.87 at trigger day and p value was > 0.001, no statistical difference in LH levels regarding the three time points between patients who get pregnant and non-pregnant women with pregnant patients having higher baseline lower antagonist starting day, and higher trigger LH levels 5.16 ± 1.87, 4.30 ± 1.72, 4.30 ± 1.72 respectively. Difference in LH level between cycle day 2 and the day of antagonist starting according to starting day of antagonist reveals that the basal LH values declined significantly (p= <0.001) until cycle day 7 of stimulation after which the basal LH start to increase and also with a high significant difference (negative values mean that the level decrease in comparison to the base line level).The comparable LH level in the current study reveals that earlier initiation of antagonist may serve no purpose and it is advisable to include the measurement of LH level to the criteria of antagonist initiation for better individualization and better outcome and to avoid un necessary earlier start of antagonist.
Successful implantation needs a receptive endometrium, a functional and normal embryo at the stage of blastocyst developmental and a synchronized dialogue between embryonic tissues and maternal tissues. The current study was planned and conducted to investigate the potential role of vaginal pessary of hyaluronic acid on intracytoplasmic sperm injection (ICSI) outcome. This study included 63 infertile women (32 women as study group receiving hyaluronic acid and 31 control group) who were subjected to ovulation induction programs with gonadotropin releasing hormone (GnRH) antagonist protocols for in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) procedures. Blood samples were taken by Vacutainer tubes and centrifuged according to the manufacturer’s instructions for the preparation of serum samples. Serum samples for Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) were obtained from each patient when the basal hormonal status was determined. The second time point is when the samples were obtained on the day of ova pickup, after that the G1 embryos will be transferred inside the uterine cavity. Then performance of endometrial receptivity parameters or patterns evaluation and patients were followed up to do pregnancy test after14 days after embryo transfer. On the day of human chorionic gonadotropin (hCG), there was no significant difference in mean serum Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) between hyaluronic acid group and reference group, respectively (p = 0.824). There was no significant difference in mean follicular fluid Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) between the hyaluronic acid group and reference group, 0.92 ±0.36 pg/ml versus 0.82 ±0.22 pg/ml, respectively (p = 0.223). Treatment with the hyaluronic acid resulted in non-significant increase in serum and follicular fluid Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), and this increment is not related to Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) improvement in local blood endometrial blood flow as reflected by reduction in resistive index and pulsatility index with eventual improvement in pregnancy outcome.
Kisspepetin is considered as a key regulator of reproduction, through its direct role in controlling the hypothalamic pituitary gonadal axis necessary for controlling the ovulatory process and indirectly by impacting glucose heamostasis and metabolism. We aimed to examin the correlation between body mass index and level of Kisspeptin in serum and follicular fluid. This study is a cross sectional study done on (80) infertile Iraqi patients aged (18-40 years) scheduled for fresh intracytoplasmic sperm injection cycle. This study is conducted in the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies of Al-Naharin University, from September 2020 to May 2021. For each participant, the GnRH antagonist protocol was used to hyperstimulate the ovaries, and samples from serum and follicular fluid were obtained at day of oocytes retrieval for measuring Kisspeptin level using enzyme linked immunosorbent assay (ELIZA) technique. Serum and follicular fluid Kisspeptin were insignificantly increasing with the increase in the BMI (p value =0.406) (p value = 0.352) respectively. Serum and follicular kisspetin were positively and significantly correlated (r = 0.536, p value= 0.000). Serum and follicular fluid kisspeptin were numerically increasing with the body mass index of infertile women, although this increament is statically insignificant, serum kisspeptin can be used as a mirror image to follicular fluid kisspeptin as there was a statistical association between them in this study.
The aim of any given ICSI cycle is to achieve normal response and avoid poor or hyper response. A part from ovarian hyper stimulation syndrome (OHSS), pregnancy rate in hyper responder females usually low which could be related to the adverse effect of hyper estrogenic state on oocytes, embryos quality and uterine endometrium. To evaluate the effect of hyper response on ICSI outcome represented by oocytes, embryos quality, fertilization and pregnancy rates. Study showed that total number of retrieved oocytes, mature, immature oocytes, total embryos, good quality embryos and blastocyst count were significantly higher in hyper followed by normal and poor responders respectively. Fertilization rate was significantly higher in both hyper and normal responders than poor ones, while pregnancy rate was significantly higher in hyper responders 47.6% followed by normal 40.7% and then poor ones 16.7%. Conclusions: Irrespective of abnormal hormonal milieu, excessive ovarian response and higher number of produced oocytes improve ICSI outcome in hyper responder females by increasing the chance of getting higher number of embryos, good quality embryos and even blastocyst numbers which in turn increase the chance of pregnancy.
Background: Both clomiphene citrate and tamoxiphene citrate, as an anti estrogen, is the most common prescribed medication for male infertility.In humans, ant estrogens interfere with the normal negative feedback of sex steroids at the hypothalamus and pituitary, thereby increasing endogenous gonadotropin releasing hormone (GnRH) secretion from the hypothalamus and follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion directly from the pituitary. Objective: The objective of this study was to investigate the effect of clomiphene citrate (CC) and tamoxiphene citrate (TC) administered to male mice on quality of sperm motility and activity. Materials and Methods: Ninety six male mice were divided into two major groups, and every one of these groups was subdivided into three minor groups involving control and two treated groups. In the CC study, 48 mice were administrated orally 0, 0.0125 mg and 0.025 mg as control (G 1), low dose (G 2) and high dose (G 3) for 42 days. While, in the TC study, 48 mice were administrated orally 0, 0.01 mg and 0.02 mg as control (G 1), low dose (G 2) and high dose (G 3) for 42 days. Then, the male mice were sacrificed, both vas deferens were collected and assessment sperm motility and activity. Results: The results of present study appeared that the use high dose of CC or TC significantly increment (P<0.05) sperm motility and activity as compared to control groups. Conclusions: Based on the results of this study, it can be concluded that the administration of high dose of either CC or TC increases sperm motility and activity.