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.
To assess the predictive value of different clinical, laboratory, and ultrasound parameters in Letrozole when used as an ovulation induction in anovulatory infertile PCOS women. The current study was done in the secondary-referral infertility clinic in AL-Yarmouk teaching hospital, and Al-Mustansiriyah medical college. Sixty-seven anovulatory infertile women with the polycystic ovarian syndrome. Letrozole was given orally on day 2 or 3 of the menstrual cycle for five days and repeated for three consecutive cycles. The primary outcome measures were to evaluate the response rate in the form of successful ovulation and clinical pregnancy. The ovulation rate was (64.2%), with clomiphene naïve vs. previous clomiphene use; it was 87.5%, 51.2% respectively, while pregnancy rate was (32.8%), 41.6% with clomiphene naïve vs. 27.9% with previous clomiphene use. Clinical (age, BMI, Waist circumference, cycle length and days between cycle, infertility period and type, previous reproductive outcome, androgen symptom and m-FG score), laboratory (E 2 , FSH, LH, testosterone, FAI, FBS, fasting insulin, HOMA – IR, and AMH) and ultrasound (mean ovarian volume, mean AFC and antral follicular diameter) parameters were founded to affect ovulation and pregnancy in different extent. After putting all variables in a scoring system, it was found that if the patients had > 26 points for the score, it's more likely that the woman becomes pregnant. A predictive pregnancy score was developed from basic clinical, laboratory, and ultrasound parameters. It may help the clinician to individualized ovulation induction protocol in PCOS women; however, external validation of this system is recommended in a more extensive prospective study.
It was observed that embryos from oocytes resulting from well-vascularized follicles had a higher implantation rate than those from oocytes developed in poorly vascularized follicles. Neovascularization was recognized as primary in terms of ovulatory follicles growth and selection. Vascular endothelial growth factor serum level has a positive correlation with perifollicular blood flow. The 2D Color and Pulsed Doppler ultrasounds that allow visual observation of the flux of the blood in a limited part of the wall of the preovulatory follicles can be easily measured. To study the preovulatory follicle's blood flow parameters in infertile women undergoing different ovulation induction protocols. 50 infertile female patients who had undergone Intrauterine Insemination (IUI) procedures were classified into two groups which were letrozole or clomiphene citrate groups as induction protocol. Another ultrasound was performed on cycle day 11, 12, or 13 to evaluate growth follicles, also a Doppler study was done to measure perifollicular blood flow and endometrial thickness at the same time blood sample to measure vascular endothelial growth factor were taken. Human chorionic gonadotropin was injected and then after 36-40 hrs. IUI Procedure is done and follows up with the patient to do a pregnancy test after 14 days. The number of dominant follicles, endometrial thickness at HCG trigger, Perifollicular doppler blood flow vascular endothelial growth factor level, pregnancy rates were all measured in both groups. There were significant differences in Perifollicular RI (p<0.001) but there were no significant differences in Perifollicular PI (p=0.476). Regarding pregnancy rate, the letrozole group has a higher although not significant pregnancy rate (32%), if compared with those using CC (20%).
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.
Poor ovarian responders (PORs) are characterized by decreased the response of the ovaries to stimulation. Nowadays, using soft protocol of low doses of Gn with/without oral compounds such as letrozole was accepted as a good option. The endometrium receptive parameters include sub endometrial resistance, pulsatility index and endometrial thickness. Eighty infertile POR women divided to two equal groups and undergoing IVF/ICSI antagonist protocols. One group underwent soft protocol using letrozole 2.5mg twice daily for 5 days starting from cycle day 2-3 overlapped low-dose Gn (225 IU) from cycle day 4-5. Other group received high dose Gn only (450 IU) from cycle day 2-3. Both groups continued stimulation cycle until the day of trigger using the flexible antagonist protocol. Estimation of values of sub endometrial RI and PI with endometrial thickness by 2 Color Doppler ultrasound was performed at day of trigger, OCP and ET. There was no significant difference for endometrial thickness at day of trigger, OCP and ET. There was significant difference in means of sub endometrial RI and PI at day of trigger, OCP and ET (P>0.05). This study showed evidence in favor of soft protocol for POR regarding pregnancy rates in spite of the statically difference in means of sub endometrial RI and PI associated with much less cost effectiveness.
Despite developments in assisted reproductive technology, there is immaterial progress in the implantation and pregnancy rates. Intrauterine infusion (IUIF) of autologous platelet-rich plasma (PRP) might renew implantation rates through its paracrine properties by progression cytokines and growth factors which favor implantation. Here we determine whether the IUIF of autologous PRP had a role in pregnancy outcome through its outcome on epidermal growth factor and endometrial thickness. An overall of 43 patients where prospectively randomly dispersed into two groups subjected to a superovulation program using Letrozole® tablet orally 2.5 mg twice daily 12 hours apart from day 2 for 5 days for one cycle. 20 women were considered as control receiving the conventional intrauterine insemination (IUI) management while 23 of them were given PRP by IUIF on the day of human chorionic gonadotrophin injection. The IUI was done for both groups 36-48 hours after confirming ovulation. The blood samples were collected from both groups on the day of IUI for the valuation of epidermal growth factor and an ultrasound was done on the day of human chorionic gonadotrophin injection and day of IUI for assessment of endometrial thickness. The mean endometrial thickness in the PRP group at the day of IUI was significantly thicker than that of the control group and the difference in percentage change of endometrial thickness between PRP group and controls significantly higher in PRP group. The mean epidermal growth factor and the pregnancy rate were significantly superior in the PRP group than that of controls. In conclusion, autologous PRP IUIF was well-tolerated and resulted in a significant expansion in endometrial thickness, epidermal growth factor Level and, subsequent pregnancy rate in an infertile woman undergoing IUI.
Intrauterine insemination (IUI) comprises the insertion of a high number of washed and processed spermatozoa directly into the cervix to the uterine cavity around the time of ovulation to increase the chances of pregnancy. It is usually used for couples with mild male factor infertility, unexplained infertility, cervical factors, mild endometriosis, and psychological, sexual dysfunction. The endometrium, which lines the uterus, is prepared for the implantation of the embryo; this process starts in the proliferative phase and extends throughout the luteal phase. Implantation, a crucial phase of pregnancy, is a complicated process, and more than half of failures to achieve pregnancy are caused by implantation failure. To assess the influence of endometrial flushing of 1000IU hCG done prior to IUI procedure on pregnancy rate in infertile females undergoing IUI treatment. The present study was applied to 80 infertile subjected to ovarian stimulation protocol using letrozole and hMG in doses adjusted according to their response; triggering was done using subcutaneous HCG. The results of the present study showed no significant difference regarding initial characteristics, indication for IUI, basal menstrual cycle characteristics, ovarian stimulation characteristics, and semen parameters before and after processing, while there was a significant difference between both groups regarding biochemical and clinical pregnancy rates. In IUI cycles, endometrial human chorionic gonadotropin (hCG) flushing done 5-10 minutes prior to IUI can improve biochemical and clinical pregnancy rates.