Clomiphene citrate plus letrozole versus clomiphene citrate alone for ovulation induction in infertile women with ovulatory dysfunction: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the efficacy of the combination of clomiphene citrate (CC) and letrozole to that of CC alone in inducing ovulation in infertile women with ovulatory dysfunction. METHODS: A randomized controlled trial was conducted at a single academic medical center between November 2020 and December 2021. Anovulatory infertility females, aged 18 to 40, were evenly distributed by a computer-generated block of four into two treatment groups. A "combination group" received a daily dose of CC (50 mg) and letrozole (2.5 mg), while a "CC-alone group" received a daily dose of CC alone (50 mg). The study medications were administered on days 3 through 7 of menstrual cycle. The primary outcome was the ovulation rate, defined by serum progesterone levels exceeding 3 ng/mL at the mid-luteal phase. The secondary outcomes were ovulation induction cycle characteristics, endometrial thickness, conception rate, and adverse events. RESULTS: One hundred women (50 per group) were enrolled in the study. The mean age was not significantly different in both groups: 31.8 years in the combination group and 32.4 years in the CC-alone groups (P = 0.54). The prevalence of polycystic ovary syndrome in the combination and CC-alone groups was 48% and 44%, respectively (P = 0.841). According to intention-to-treat analysis, the ovulation rates were 78% and 70% in the combination and CC-alone groups, respectively (P > 0.05). There was no significant difference in the mean endometrial thickness or the number of dominant follicles of the groups. No serious adverse events were observed in either group. CONCLUSIONS: Our study found no significant difference between the combination of CC and letrozole and CC alone in inducing ovulation in infertile women with ovulatory dysfunction in one cycle. The small number of live births precluded any meaningful statistical analysis. Further studies are needed to validate and extend our findings beyond the scope of the current study. TRIAL REGISTRATION: The study was registered at https://www.thaiclinicaltrials.org with the following number: TCTR20201108004 and was approved on 08/11/2020.

Pregnancy outcomes after vaginal probiotic supplementation before frozen embryo transfer: a randomized controlled study.

In women receiving assisted reproductive treatment, intrauterine lactobacilli dominance has been associated with higher rates of pregnancy achievement. This randomized controlled trial conducted in the fertility clinic of the university hospital from 7 August 2019 to May 2021, aimed to compare the clinical outcome of embryo transfer in frozen-thaw cycles with Lactobacillus supplementation prior to embryo transfer and the standard treatment. A total of 340 infertile women underwent randomization. The biochemical and clinical pregnancy rates were comparable between the groups (39.9 and 34.2% in the study group vs. 41.8 and 31.7% in the control group); however, the miscarriage rate was significantly decreased in the study group (9.5 vs. 19.1%, respectively, p = 0.02), [OR = 0.44, 95% CI (0.23, 0.86)]. Among 49 women diagnosed with bacterial vaginosis, the live birth rate in the study group was higher than the control group (42.31 vs. 26.09%, p = 0.23), [OR = 2.08, 95% CI (0.62, 6.99)]. In the blastocyst transfer group (n = 206), the live birth rate was significantly higher in the study group than in the control group (35.71 vs. 22.22%, p = 0.03) [OR = 1.9, 95% CI (1.05, 3.59)]. Therefore, intravaginal lactobacilli supplementation before embryo transfer in the frozen-thaw cycle did not improve the biochemical and clinical pregnancy rate in the general population but significantly reduced the miscarriage rate.Trial Registration: TCTR20190429001 (29/04/2019) @ www.thaiclinicaltrials.org .

Comparison of pregnancy outcomes using a time-lapse monitoring system for embryo incubation versus a conventional incubator in in vitro fertilization: An age-stratification analysis.

OBJECTIVE: The aim of this study was to compare the pregnancy outcomes of in vitro fertilization with embryo transfer between embryos cultured in a time-lapse monitoring system (TLS) and those cultured in a conventional incubator (CI). METHODS: The medical records of 250 fertilized embryos from 141 patients undergoing infertility treatment with assisted reproductive technology at a tertiary hospital from June 2018 to May 2020 were reviewed. The study population was divided into TLS and CI groups at a 1 to 1 ratio (125 embryos per group). The primary outcome was the live birth rate. RESULTS: The TLS group had a significantly higher clinical pregnancy rate (46.4% vs. 27.2%, p=0.002), implantation rate (27.1% vs. 12.0%, p=0.004), and live birth rate (32.0% vs. 18.4%, p=0.013) than the CI group. Furthermore, subgroup analyses of the clinical pregnancy rate and live birth rate in the different age groups favored the TLS group. However, this difference only reached statistical significance in the live birth rate in women aged over 40 years and the clinical pregnancy rate in women aged 35-40 years (p=0.048 and p=0.031, respectively). The miscarriage rate, cleavage rate, and blastocyst rate were comparable. CONCLUSION: TLS application improved the live birth rate, implantation rate, and clinical pregnancy rate, particularly in the advanced age group in this study, while the other reproductive outcomes were comparable. Large randomized controlled trials are needed to further explore the ramifications of these findings, especially in different age groups.

Ultrasound guidance versus the classical method for intrauterine insemination in oral medication-stimulated cycles: A randomized, single-blind, controlled trial.

OBJECTIVE: This study was conducted to compare the pregnancy rates of ultrasound-guided intrauterine insemination (UG-IUI) and classical intrauterine insemination (C-IUI) cycles. STUDY DESIGN: A total of 320 infertile women were enrolled and randomized into an UG-IUI group, and a C-IUI group. All participants received an oral medication for ovarian stimulation. With both groups, the IUIs were scheduled and performed by doctors in their residency and fellowship training, under supervision. The duration and difficulty of the procedures were assessed. A pregnancy test was offered 3 weeks later if the participants did not have menstruation. RESULTS: The demographic and other baseline characteristics of the groups (baseline hormone levels, cervical length, uterine position, endometrial thickness, and expertise of the providers) were comparable. The pregnancy rates were similar, with 6.9 % and 6.3 % for the UG-IUI and C-IUI groups, respectively. In the UG-IUI group, the pregnancy rate of the multigravida women was three times higher than that of the nulligravida women (15.4 % vs. 5.0 %; p = 0.13). Although the duration of the procedure was shorter for the UG-IUI group (p < 0.05), the level of difficulty was similar for the two groups. CONCLUSIONS: For oral-medication stimulated cycles, UG-IUI did not increase the pregnancy rate more than with C-IUI. However, the pregnancy rate tended to increase with UG-IUI for multigravida women.

Increased implantation rate after intrauterine infusion of a small volume of human chorionic gonadotropin at the time of embryo transfer: a randomized, double-blind controlled study.

PURPOSE: Intrauterine human chorionic gonadotropin (hCG) infusion at the time of embryo transfer (ET) has resulted in controversial results. We evaluated the effects of intrauterine infusion of a small volume of hCG at the time of ET in fresh and frozen-thawed cycles. METHODS: Infertile women scheduled for ET with either fresh or frozen-thawed cycles were enrolled and randomized into two groups (n = 100 each): an hCG group, who received 500 IU of hCG in 10 µL culture medium infused into the uterine cavity using a soft catheter 4 min before ET; and a control group, who received 10 µL of culture medium alone by the same technique. The primary outcome was the implantation rate. The secondary outcomes were clinical pregnancy and live birth rate. RESULTS: Two hundred infertile women aged 18-43 years, undergoing fresh or frozen-thawed ET were enrolled, regardless of any previous transfer cycles. The implantation rate was significantly higher in the hCG group compared with the control group (28.8% vs. 18.2%, p = 0.030). The clinical pregnancy rates were similar in both groups (42% vs. 30%, p = 0.077). The live birth rates were also similar (29% and 23% in the hCG and control group, respectively). CONCLUSIONS: Intrauterine infusion of a small volume of hCG at the time of ET can significantly improve the implantation rate, while the clinical pregnancy rate may only be improved in younger patients (aged < 40 years). This technique may thus be of benefit to patients undergoing clinical infertility treatment.

Application of testosterone supplementation in semen to improve sperm motility in asthenozoospermic males.

PURPOSE: To evaluate the effect of different concentrations and durations of seminal testosterone supplementation upon the motility of sperm from asthenozoospermic males. METHODS: Semen was collected from 41 infertile men with asthenozoospermia. After liquefaction, 200 µL was extracted from each semen sample and divided equally into five groups for a negative control, a vehicle control, and three experimental portions mixed with 4.75, 7.75, and 17.75 nmol/L of testosterone, respectively. The sperm motility was evaluated at 5, 15, 30, and 45 min following the addition of testosterone. The supernatant from remaining samples were sent for testosterone assay. Sperm viability was also evaluated after 45 min. RESULTS: There was no difference in the number of samples in each group which showed a 20% improvement in sperm motility. Group 3 showed a significant retardation in the reduction of motility compared with Group 5 (P < 0.05). Semen samples with a final testosterone concentration of 4.51-10 nmol/L showed a significant improvement in sperm motility when measured 5 min after addition. In contrast, samples showing a rise in testosterone level above 10 nmol/L were associated with a reduction in both sperm motility and viability. CONCLUSION: Despite sperm motility decreasing over time, supplementation of semen samples with 4.75 nmol/L of testosterone could delay such reduction. A final seminal testosterone concentration of 4.51-10 nmol/L appears to be optimal for the best sperm motility.

The correlation of cumulus mucification patterns with oocyte maturation rate in vitro in FSH + LH-primed IVM cycles: a prospective study.

PURPOSE: This prospective study was conducted to compare the oocyte maturation rate in vitro among four types of cumulus cell (CC) morphology, in dual gonadotropin-primed in vitro maturation (IVM) oocyte cycles. METHODS: Two-hundred and thirty cumulus-oocyte complexes (COCs) were retrieved from FSH + hCG-primed in vitro maturation cycles of 20 patients diagnosed with polycystic ovarian syndrome. The COCs that contained immature oocytes were classified into four groups according to their cumulus mucification patterns (dispersed, clumped, compacted or sparse) and their oocyte maturation rates were compared. Chi square test and Fisher's exact test were used as appropriate. RESULTS: Oocytes enclosed by dispersed and clumped CCs exhibited higher maturation rates than those with compacted and sparse patterns (P < 0.001). CONCLUSION: In dual gonadotropin-primed IVM cycles, oocyte maturation rates are highest in those showing dispersed and clumped CC patterns.

Outcomes of follicle-stimulating hormone priming and nonpriming in in vitro maturation of oocytes in infertile women with polycystic ovarian syndrome: a single-blinded randomized study.

BACKGROUND/AIMS: Follicle-stimulating hormone (FSH) priming has been studied in in vitro matured oocytes for oocyte maturation rate, embryo quality, and pregnancy rate with discouraging results. This study aimed to initiate FSH stimulation later, i.e. on day 6, to prolong natural endometrial priming and promote oocyte maturation. METHODS: Forty polycystic ovarian syndrome (PCOS) patients were enrolled into a single, blinded (investigator), randomized, controlled study, and randomly allocated to group 1 (no FSH priming) or group 2 (day 6 recombinant FSH priming). Oocytes were retrieved after human chorionic gonadotropin injection on day 10. After 27 or 51 h of incubation, only mature oocytes were denuded and fertilized by intracytoplasmic sperm injection. Two day 3 embryos were transferred in most patients. Rates of oocyte maturation, cleavage, and pregnancy were compared. RESULTS: The oocyte maturation rates within 51 h were 62.6 and 72.7% in groups 1 and 2, respectively (p < 0.01). The embryo cleavage rate was significantly higher in group 2 than in group 1 (77.3 vs. 63.6%, p < 0.05). The pregnancy rate was higher in group 1 than in group 2 (50 vs. 30%, p > 0.05). CONCLUSION: FSH priming is beneficial for promotion of the maturation and quality of oocytes, leading to a higher embryo cleavage rate and lower rate of pregnancy loss.

Sperm preparation before freezing improves sperm motility and reduces apoptosis in post-freezing-thawing sperm compared with post-thawing sperm preparation.

PURPOSE: To evaluate whether sperm preparation (swim-up technique) before freezing improves the percentages of sperm motility, sperm viability, and non-apoptotic spermatozoa after freezing-thawing process compared with preparation after cryopreservation. METHODS: Semen samples from 65 infertile males were equally divided into two aliquots one of which was processed for swim-up prior to cryopreservation and one of which was processed following cryopreservation. Sperm count, motility, and apoptosis index were measured in each group. RESULT (S): The total sperm count and the total motile sperm count decreased after thawing in both the pre-preparation and non-preparation groups compared with neat semen group (P < 0.001). Moreover, the percentage of apoptotic sperm in the pre-preparation group after cryopreservation was lower than that in the non-preparation group (P < 0.05), whereas the percentage of vital sperm with progressive motility was higher than that in the pre-preparation group (P < 0.001). CONCLUSION (S): Semen preparation by swim-up before freezing resulted in better sperm quality and fewer apoptotic sperm than sperm preparation after thawing. Therefore, sperm preparation before cryopreservation should be considered in routine sperm cryopreservation.

Efficacy of mefenamic acid and hyoscine for pain relief during saline infusion sonohysterography in infertile women: a double blind randomized controlled trial.

OBJECTIVES: To evaluate the efficacy and level of satisfaction from mefenamic acid and hyoscine when used for pain relief during saline infusion sonohysterography. STUDY DESIGN: In this double blind randomized controlled trial, 141 nulliparous women were allocated to receive 500 mg of mefenamic acid, 10mg of hyoscine or a placebo, which was packed in the same outer capsule. Saline infusion sonohysterography (SIS) was performed 30 min later by one operator. Pain and satisfaction scores were evaluated using a 10 cm visual analog scale. Baseline characteristics, pain and satisfaction scores were compared among the three groups. Pain scores were recorded before, after catheter insertion, during, immediately after, and 30 min after the procedure. RESULTS: No statistically significant differences were found in baseline characteristics, pain and satisfaction scores among the three groups. Maximum pain during SIS was 4.40 ± 3.34, 4.67 ± 3.14 and 4.85 ± 3.19 in the mefenamic acid, hyoscine and placebo groups respectively. There was a 31.1% prevalence of intrauterine abnormality and the most frequent finding was endometrial polyp. CONCLUSION: There is no benefit in using mefenamic acid and hyoscine in the prevention of pain occurring from SIS.

The successful pregnancy and birth of a healthy baby after human blastocyst vitrification using Cryo-E, first case in Siriraj Hospital.

This case report illustrates a successful pregnancy and birth after vitrification of a human blastocyst using modified cryostorage- Cryo E. A 31-year-old woman underwent short protocol for ovarian hyperstimulation in an IVF treatment program. After administration of intramuscular hCG, all oocytes were recovered transvaginally with ultrasound guidance. Twelve mature oocytes were obtained and eight were fertilized Three out of eight embryos became blastocyst, and two blastocysts were transferred on day 5, but no implantation occurred The other was cryopreserved by vitrification technique using a cryo E. Three months after freezing, the cryopreserved blastocyst was thawed and survived. It was transferred to the patient's uterus. Blastocyst implantation resulted in a healthy single pregnancy. After continuing pregnancy until term, she delivered by cesarean section due to unfavorable cervical conditions. A male baby with Apgar score 9/10, weighing 3500 g was born. Her child showed normal growth.

Outcome of sperm preparation using double-gradients technique study in Siriraj Hospital.

OBJECTIVE: To determine the succession of sperm preparation using the double-gradients technique on sperm quality: sperm recovery rate, sperm concentration, sperm motility and percentage of post wash total motile sperm count. STUDY DESIGN: Retrospective descriptive study. SETTINGS: Infertility clinic, Faculty of Medicine, Siriraj hospital. MATERIAL AND METHOD: During the period of January 1, 2002 through December 31, 2007, data including semen analysis before and after IUI procedure were reviewed in all male patients who were referred to the andrology laboratory for sperm washing and IUI. Comparison of semen parameters such as total sperm concentration, total motile sperm count before and after sperm preparation as well as total sperm recovery rate and total motile sperm recovery rate was evaluated. RESULTS: After sperm preparation, both sperm concentration and progressive sperm motility significantly increased, while total motile sperm count significantly decreased. Moreover, the percentage of motile sperm recovery rate and total sperm recovery rate was higher after sperm preparation at around 59.88 +/- 19.26% and 34.03 +/- 14.58% respectively. When categorizing semen parameters to 4 groups: normozoospermia, oligozoospermia, astenozo-ospermia and oligo-astenozoospermia, sperm motility in each group, comparing with sperm motility prior preparation, significantly improved after sperm preparation. Furthermore, motile sperm recovery rate in each group significantly increased except for astenozoospermia. Total sperm recovery rate in oligozoospermia was significantly higher than normozoospermia, yet the others were significantly lower. CONCLUSION: Sperm preparation using double gradient percoll provided a high percentage of motile sperm recovery rate and total sperm recovery rate. It also dramatically improved progressive sperm motility in normozoospermia, oligozoospermia, astenozoospermia and oligo-astenozoospermia.

Comparison between sperm treated with pentoxifylline and 2-deoxyadenosine using hypo-osmotic swelling test.

OBJECTIVE: To compare the percentage of sperm tail membrane swelling under hypo-osmotic conditions between sperm treated with pentoxifylline and 2-deoxyadenosine. DESIGN: Experimental in vitro study. MATERIAL AND METHOD: Thirty normal semen samples from male partners of infertile couples were collected. After sperm preparation by two-layer Percoll gradient method, each sperm sample was divided into three specimens. Pentoxifylline and 2-deoxyadenosine were separately added into two specimens, while the third specimen was used as a control. Hypo-osmotic swelling test was performed in all specimens. Percentage of swollen spermatozoa in each specimen was evaluated. RESULTS: The mean percentage of swollen spermatozoa in the semen samples supplemented with pentoxifylline and 2-deoxyadenosine were both significantly higher than those in the control (82.8 +/- 7.7 and 83.0 +/- 9.5 vs 70.8 +/- 12.7; p < 0.001). There was no significant differences of swollen spermatozoa between pentoxifylline and 2-deoxyadenosine (p = 0.898). CONCLUSION: Addition of pentoxifylline and 2-deoxyadenosine to the sperm prepared by the two-layer Percoll gradient method can almost equally enhance the sperm membrane integrity. Therefore, it may be beneficial to add these compounds to sperm preparation for use in assisted reproduction.