Pregnancy outcome in delayed start antagonist versus microdose flare GnRH agonist protocol in poor responders undergoing IVF/ICSI: an RCT

Background: Over the years, many article on different aspects of pathogenesis and management of poor ovarian responders have been published but there is no clear guideline for treating themyet

Objective: This study was designated to compare the effectiveness of a delayed start protocol with gonadotropin-releasing hormone [GnRH] antagonist and microdose flare-up GnRH agonist protocol in poor ovarian responders

Materials and Methods: This randomized clinical trial consisted of 100 poor ovarian responder women in assisted reproductive technologies cycles. They were divided randomly in delayed-start antagonist protocol [with estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation] and microdose flare-up GnRH agonist protocol. The main outcome was clinical pregnancy rate and second outcome was the number of retrieved oocytes, mature oocytes, 2PN number, fertilization rate, and implantation rate

Results: Fertilization rate, clinical pregnancy rate, and ongoing pregnancy rates were not significantly different between the two studied protocols. Number of retrieved oocytes [5.10+/-3.41 vs. 3.08+/-2.51] with p=0.002, mature oocytes [4.32+/-2.69 vs. 2.34+/-1.80] with p=0.003, number of 2PN [3.94+/-1.80 vs. 2.20+/-1.01] with p=0.001 and implantation rate [19.40% vs. 10.30%] with p=0.022 were significantly higher in delayed antagonist group

Conclusion: The delayed-start protocol can improve ovarian response in poor responders by stimulating and synchronizing follicle development

effect of 24 hours delay in oocyte maturation triggering in IVF/ICSI cycles with antagonist protocol and not-elevated progesterone: a randomized control trial

Background: The best time of final oocyte maturation triggering in assisted reproduction technology protocols is unknown. This time always estimated by combined follicular size and blood progesterone level

Objective: The aim of this study was evaluation of the effect of delaying oocyte maturation triggering by 24 hr on the number of mature oocytes [MII] and other in vitro fertilization cycle characteristics in antagonist protocols with not-elevated progesterone [p

Materials and Methods: All patients' candidate for assisted reproduction technology underwent controlled ovarian hyperstimulation by antagonist protocol. When at least 3 follicles with >/=18 mm diameters were seen by vaginal ultrasonography; blood progesterone level was measured. The patients who had progesterone level

Results: Number of retrieved oocytes, mature oocytes [MII], fertilized oocytes [2PN], embryos formation, number of transferred embryos and embryos quality has not significant differences between two groups. Also, fertilization and implantation rate, chemical and clinical pregnancy did not differ between groups

Conclusion: Delaying of triggering oocyte maturation by 24 hr in antagonist protocol with not-elevated progesterone [progesterone

Effect of adding human chorionic gonadotropin to frozen thawed embryo transfer cycles with history of thin endometrium

Background: Embryo implantation process is a complex phenomenon and depends on fetal and maternal factors interaction. Endometrial thickness is needed for successful implantation

Objective: We designed this study in order to assess adding human chorionic gonadotropin [HCG] to the conventional protocol in endometrial preparation in women with thin endometrium and a history of in vitro fertilization-embryo transfer [IVF-ET] failure

Materials and Methods: The non-randomized clinical trial study [quasi experimental design] was performed on 28 patients. Participants were women who were candidate for frozen-thawed [ET] and had two previous failed ET cycles because of thin endometrial. HCG was administrated [150 IU, intramuscular] from the 8th day of cycle and when endometrial thickness reached at least 7mm HCG was discontinued and frozen thawed ET was done

Results: Totally 28 patients were included. The mean +/- SD age of participants was 30.39 +/- 4.7. The mean of endometrium thickness before and after HCG were 5.07 +/- 0.43 and 7.85 +/- 0.52, respectively p<0.001. Also, there were five clinically and chemically pregnant women

Conclusion: The findings of the study suggested that adding HCG to the conventional preparation method was an effective protocol and significantly improved endometrial thickness and pregnancy outcomes in women with previous embryo transfer failure because of thin endometrium

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 17 beta-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 microg 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

Effects of single dose GnRH agonist as luteal support on pregnancy outcome in frozen-thawed embryo transfer cycles: an RCT

There is no doubt that luteal phase support is essential to enhance the reproductive outcome in IVF cycles. In addition to progesterone and human chorionic gonadotropin, several studies have described GnRH agonists as luteal phase support to improve implantation rate, pregnancy rate and live birth rate, whereas other studies showed dissimilar conclusions. All of these studies have been done in fresh IVF cycles. To determine whether an additional GnRH agonist administered at the time of implantation for luteal phase support in frozen-thawed embryo transfer [FET] improves the embryo developmental potential. This is a prospective controlled trial study in 200 FET cycles, patients were randomized on the day of embryo transfer into group 1 [n=100] to whom a single dose of GnRH agonist [0.1 mg triptorelin] was administered three days after transfer and group 2 [n=100], who did not receive agonist. Both groups received daily vaginal progesterone suppositories plus estradiol valerate 6 mg daily. Primary outcome measure was clinical pregnancy rate. Secondary outcome measures were implantation rate, chemical, ongoing pregnancy rate and abortion rate. A total of 200 FET cycles were analyzed. Demographic data and embryo quality were comparable between two groups. No statistically significant difference in clinical and ongoing pregnancy rates was observed between the two groups [26% versus 21%, p=0.40 and 21% versus 17%, p=0.37, respectively]. Administration of a subcutaneous GnRH agonist at the time of implantation does not increase clinical or ongoing pregnancy

Efficacy of prophylactic dexamethasone in prevention of postoperative nausea and vomiting

Objective Many trials have been conducted with regard to the relative benefits of prophylactic anti-emetic interventions given alone or in combination, yet the results remain unknown. This study reviewed the efficacy of a single prophylactic dose of dexamethasone on postoperative nausea or vomiting [PONV] after abdominal hysterectomy. Methods In a prospective study of 100 women undergoing total abdominal hysterectomy [TAH] under general anesthesia, the dexamethasone group [n = 50] received a single dose [8 mg] immediately after the operation, and the saline group [n = 50] received a dose of saline as a placebo, in addition to conventional management. The incidence of nausea, vomiting, the need for an anti-emetic and patient satisfaction with the management of PONV were evaluated during the first 24 postoperative hours. Results The overall frequency of nausea during the initial postoperative 24 in the dexamethasone and saline groups were 12% and 18%, respectively, and vomiting was 10% and 16%, respectively [P = 0.001]. However, there was a lower need for a rescue anti-emetic drugs in the dexamethasone group [18% vs 24%], but it was not statistically significant [P = 0.06]. Conclusion The results of this study indicate that a single prophylactic dose of dexamethasone after an operation can reduce postoperative nauseaandvomiting

Comparison of pregnancy outcome after letrozole versus clomiphene treatment for mild ovarian stimulation protocol in poor responders

Poor ovarian response to controlled ovarian stimulation is one of the most important interest points in assisted reproduction. Mild ovarian stimulation seems to be preferable to high dose of FSH regimens in women with a history of poor ovarian response in previous protocol. Clomiphene citrate and letrozole alone or in combination with FSH have been used in mild ovarian stimulation protocol. To compare the efficacy of letrozole and clomiphene citrate for mild ovarian stimulation on assisted reproductive technology outcomes in poor responders. In a randomized control study, 184 women aged between 20 and 45 years with the history of poor response to ovarian stimulation who were candidate for ART were randomly subdivided into two groups: group I [n= 80], women who underwent the clomiphene/gonadotropin/antagonist protocol; and group II [n= 87], patients who underwent the letrozole/gonadotropin/antagonist protocol. Groups were compared regarding implantation, chemical and clinical pregnancy rates, There was a significant difference in the mean endometrial thickness between two groups [9.16 +/- 1.2 mm vs. 83 +/- 0.3 mm]. The implantation rate was significantly higher in letrozole group compare to clomiphene group [7.2 vs. 6.6%, p=0.024 respectively]. No significant differences were found in chemical and clinical pregnancy rate between two groups. In mild ovarian stimulation protocol, letrozole and clomiphene have similar value for the poor responder. The optimal treatment strategy for these patients remains debated

luteinizing hormone beta-subunit exon 3 [Gly102Ser] gene mutation and ovarian responses to controlled ovarian hyperstimulation

Despite extensive progress in IVF techniques, one of the most difficult problems is the variability in the response to controlled ovarian hyperstimulation [COH]. Recent studies show the effects of individual genetic variability on COH outcome. To evaluate the correlation between LHbeta G1502A polymorphisms in exon 3 of the LH gene and ovarian response to COH. A total of 220 women treated with a long protocol for ovarian stimulation were studied. Three genotypes of GG, GA and AA were detected by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] analysis. In total, 34 [17%] patients were poor responders, 154 [77%] were normal responders and 12 [6%] were hyper responders. The most frequent genotype was GA [55.5%] whereas 44.5% of patients showed GG genotype and there was no patient with AA genotype. In total 54.5% of normal responders, 61.8% of poor responders and 50% of hyper responders showed GA genotype. Our results did not establish a significant relationship between this polymorphism and the ovarian response. Therefore it is still very difficult to use the genotype of patients for prediction of the ovarian response to stimulation

Elevated serum progesterone/ MII oocyte ratio on the day of human chorionic gonadotropin administration can predict impaired endometrial receptivity

Increased serum progesterone on the day of human chorionic gonadotropin administration may affect in vitro fertilization [IVF] outcome. The aim of this study was to evaluate whether progesterone elevation on the day of human chorionic gonadotropin administration is associated with poor IVF outcome. To determine the relationship between serum progesterone on the day of HCG and the outcome of IVF-embryo transfer treatment, 378 infertile patients undergoing IVF-embryo transfer at Yazd Research and Clinical Center for Infertility from October 2009 to March 2011 were prospectively studied. In this study, absolute p-value and P/E[2] ratio were not a good predictor outcome of in-vitro fertilization but progesterone per metaphase II were predictive of implantation rate and pregnancy rate with statistically significant results but had no effect on the fertilization rate. We suggest avoided the increased progesterone that the cause of advanced endometrial maturation and impaired endometrial receptivity. If the progesterone is greater than 0.32 per oocyte metaphase II, the embryo transfer can be canceled and freezing all embryos for future transfer must be considered, to increase acceptance of the endometrium and thus increase the success rate

Effect of sildenafil citrate on endometrial preparation and outcome of frozen-thawed embryo transfer cycles: a randomized clinical trial

Background: sildenafil citrate may increase endometrial thickness and affect the outcome of frozen-thawed embryo transfer cycles

Objective: the aim of this study was to estimate the effect of sildenafil citrate on ultrasonographic endometrial thickness and pattern and to investigate the estrogen level on the day of progesterone administration, the implantation rate and chemical pregnancy rate in frozen embryo transfer cycles

Materials and Methods: this randomized controlled trial was conducted on 80 patients who had an antecedent of poor endometrial response and frozen embryos. 40 patients were given estradiol by a step up method with menstruation to prepare the endometrium, and the other 40 were given sildenafil citrate tablets [50 mg] daily in addition to the above treatment protocol from the first day of the cycle until the day progesterone was started. This was discontinued 48-72 hours prior to the embryo transfer

Results: the endometrial thickness was significantly higher in the sildenafil citrate group [p<0.0001], the triple line patterns of the endometrium were significantly higher in the sildenafil citrate group [p<0.0001], while the intermediate patterns of the endometrium were not significantly different in the two groups. The echogen patterns of the endometrium were significantly higher in control group [p<0.0001]. Finally, implantation rate and the chemical pregnancy rates were higher in the sildenafil citrate group but not significantly

Conclusion: as our study shows, the oral use of sildenafil citrate is a good way to improve the endometrial receptivity. We recommend the routine use of oral sildenafil citrate in patients with a previous failure of assisted reproduction technology cycles due to poor endometrial thickness

Metformin-letrozole in comparison with metforminclomiphene citrate in clomiphene-resistance PCOS patients undergoing IUI

Polycystic ovary syndrome [PCOS] is associated with approximately 75% of women who suffer from infertility due to anovulation. Additionally, around 20-25% of anovulatory women with PCOS do not respond at all to clomiphene citrate and are considered to be "clomiphene-resistant". Aromatase inhibitors have been suggested as an alternative treatment to clomiphene as the discrepancy between ovulation and pregnancy rates with clomiphene citrate has been attributed to its anti-estrogenic action and estrogen receptor depletion. The aim of this study is to compare results of Metformin-letrozole with Metformin-clomiphene citrate in clomiphene resistance PCOS patients undergoing IUI. In this single blind randomized trial, ovarian cycles were studied in 100 clomiphene- resistant patients with PCOS. The inclusion criteria were patients who received 150mg clomiphene citrate daily for 3 cycles and failed to become pregnant. The patients were matched for their age, body mass index [BMI], and infertility period. They were randomly allocated to a metformin-letrozole group [n=50] and a metformin-clomiphene citrate group [n=50]. Chemical and clinical pregnancies were assessed after IUI. Abortion rates were determined in both groups. Regarding pregnancy rate, there was no significant difference between the two groups. One miscarriage [2%] occurred in the metformin-clomiphene citrate group, whereas none was seen in the metformin-letrozole group. There is no significant difference in pregnancy rate between clomiphene citrate and letrozole groups although it has been 2% in the former and 5% in the latter

Remifentanil versus fentanyl for assisted reproductive technologies: effect on hemodynamic recovery from anesthesia and outcome of ART cycles

We conducted this study to compare the outcome of assisted reproductive technology [ART] procedures and recovery from anesthesia in women who received opioid analgesia with remifentanil versus fentanyl. This double-blind, randomized clinical trial was carried out in the Yazd Research and Clinical Center for Infertility, Yazd, Iran. We studied 145 women who were participants in an ART program. During the first phase of the study, all patients underwent induction of anesthesia with thiopental and received analgesia with remifentanil or fentanyl. The primary endpoint was pregnancy rate per transfer. The numbers of oocytes collected, fertilized and cleaved were recorded, as was the number of oocytes transferred and recovery profile. In the second phase of the study, all patients were followed for outcome of ART cycle. This study suggested that in women undergoing transvaginal ultrasound-guided oocyte retrieval procedures, the likelihood of a successful pregnancy was higher with a remifentanilbased monitored anesthesia care [MAC] technique than with a fentanyl-based MAC technique. The recovery from anesthesia was significantly better in the remifentanil group versus fentanyl group. The results of this study suggest that remifentanil in clinical practice is superior to fentanyl [Registeration Number: IRCT201009283468N3]

Pregnancy outcomes in asthmatic women

Asthma is considered to be the most common respiratory disorder complicating pregnancy. Seventysix asthmatic and 152 non-asthmatic pregnant women were studied. Maternal asthma was significantly associated with adverse infant outcomes, including prematurity, low birth weight and the need for Cesarean delivery. The results of this study could indicate that pregnant women with asthma were at substantially increased risk for adverse infant outcomes and suggest the need for extra attention to mothers with asthma before and during pregnancy

Comparison of the success rate of letrozole and clomiphene citrate in women undergoing intrauterine insemination

This study was conducted to compare the success rate of daily administration of aromatase inhibitor letrozole at a dose of 5 mg when administrating clomiphene citrate [CC] 100 mg daily in women undergoing superovulation and IUI. This prospective randomized trial was done in Research and Clinical Center for Infertility [Shahid Sadoughi University], Yazd, Iran. Ninety-five patients with unexplained and mild male factor infertility were studied. Using a computer-generated random table, the patients were randomized into two groups, which were treated with 5 mg of letrozole daily [42 patients, 42 cycles] or 100 mg of CC daily [53 patients, 53 cycles]. The data were analyzed using Student's t-test and chi square test. The mean age and duration of infertility in both groups were similar. There was a significant difference between the two groups in the total numbers of follicles during stimulation [5.45 +/- 4.2 in CC group vs. 3.07 +/- 2.1 in letrozole group] [P = 0.01]. No significant difference in the endometrial thickness was found between the two groups [letrozole group = 6.9 +/- 2.2, CC group = 7.8 +/- 1.8]. The mean levels of LH and FSH in both groups were similar. P value of difference in hormone levels between two groups were 0.33 and 0.47, respectively, but there was a significant difference in mean E2 levels between the two groups [241.28 +/- 167.537 in letrozole group vs. 867.34 +/- 296.689 in CC group] [P = 0.018]. The mean number of gonadotropin ampules used in both groups was the same. Pregnancy rate per cycle was 9.5% in the letrozole group and 5.7% in the CC group [P = 0.6]. Two out of the three pregnancies in the CC group [66.6%] and one out of the four pregnancies in the letrozole group resulted in a miscarriage [25%]. One twin pregnancy [33%] occurred in the letrozole group and none in the CC group. Ovarian hyperstimulation syndrome [OHSS] did not occur in either of the two groups. In IUI, superovulation with clomiphene citrate and letrozole was associated with similar pregnancy rates, but the miscarriage rate was higher with clomiphene citrate

effect of letrozole in induction of ovulation in clomiphene resistant patients

Background: In patients with anovulatory infertility the first choice of treatment for ovulation induction is an antiestrogen, most commonly clomiphene citrate [CC]. However, 20-25% of the women are resistant to CC and do not ovulate perhaps due to antiestrogenic mechanism of the CC action, which involves long-lasting estrogen receptor [ER] depletion

Objective: The objective of the study was to mimic the action of CC without depletion of ERs by the administration of an aromatase inhibitor letrozole in a selected group of Poly Cystic Ovary [PCO] patients who demonstrated failure to ovulate after treatment with CC

Materials and Methods: 20 patients with anovulation due to polycystic ovary syndrome [PCOS], who had previously inadequately responded to CC were selected for study. The aromatase inhibitor letrozole was administered orally in a dose of 2.5 mg on days 3-7 of the menstrual cycle. Then, occurrence of ovulation, endometrial thickness, and pregnancy rates were determined. Result [s]: Only one patient had one dominant follicle [1.8 cm diameter] on day 14 of the cycle [estradiol = 200 pg/ml]. IUI was done; however, no pregnancy took place. In the remaining cases, several sonographies were done between days 9 to 15 of the cycle; however, all cycles were cancelled due to absence of a dominant follicle [>L4 cm]

Conelusion[s]: Our study did not confirm the favorable effect of letrozole for induction of ovulation in patients with clomiphene resistant PCO