Comparison of luteal phase stimulation with follicular phase stimulation in poor ovarian response: a single-blinded randomized controlled trial.

BACKGROUND: In the last decade, luteal-phase ovarian stimulation (LPOS) has been suggested as an alternative controlled ovarian stimulation (COS) protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles mainly in women with a history of poor ovarian response (POR). The present randomized controlled trial study aimed to compare the outcomes of follicular phase ovarian stimulation (FPOS) and LPOS protocols in POR cases undergoing ICSI cycles. METHODS: Seventy-eight POR patients who met the Bologna criteria and underwent an ICSI cycle were included. In this study, 39 POR cases were allocated to the FPOS group, and 39 POR cases were allocated to the LPOS group. The primary outcome was the number of metaphase II (MII) oocytes. In addition, the total number of oocytes, number of top-quality day 3 embryo, day 3 embryo development rate, chemical pregnancy and clinical pregnancy rates were defined as secondary outcomes. RESULTS: The obtained results demonstrated that the number of MII oocytes significantly increased in the LPOS group compared to the FPOS group (P = 0.007). However, there was no significant difference between the two groups regarding the number of GV and MI oocytes, number of top-quality day 3 embryos and day 3 embryo development rate among both categories of patients. Also, the number of total and MII oocytes was significantly higher in the LPOS group (P = 0.016). CONCLUSION: These results suggest that LPOS protocol effectively increases the number of mature oocytes in women with a history of POR. TRIAL REGISTRATION: IRCT20210405050852N1 (Registered at Iranian registry of clinical trials; available at https://en.irct.ir/trial/55402 ).

Histological Evaluation of Products of Conception, Who Benefits from It?

Background: Histopathological evaluation of the first trimester pregnancy loss has always been controversial. Although it is recommended, it is not a part of guidelines.Methods: Six hundred eighty-six samples in a referral infertility clinic were evaluated microscopically and categorized. Two hundred ninety-five cases were evaluated by genetic methods (Multiplex Ligation-dependent Probe Amplification).Results: From 569 samples with chorionic villi, 361 cases had history of three or more abortions. 18.3% of this group showed chronic intervillous of unknown etiology (CIUE) and 8.3% revealed intervilli fibrin deposition, both pathologies with a high risk of recurrence. History of a live child was significantly higher in CIUE group. 29% of genetically evaluated cases had a chromosomal abnormality.Conclusion: Histological evaluation of recurrent pregnancy loss could illuminate the cause of abortion in relatively acceptable percentage of cases, especially in mothers with higher number of previous abortion, mothers with a history of live child and in referral centers.

The effect of low-molecular-weight heparin on live birth rate of patients with unexplained early recurrent pregnancy loss: A two-arm randomized clinical trial.

Background: The effect of anticoagulant medication in unexplained early recurrent pregnancy loss (RPL) patients is controversial. This clinical trial evaluated the effect of low-molecular-weight heparin (LMWH) on pregnancy outcomes in these patients. Materials and Methods: The study was performed as a single-blind randomized clinical trial between 2016 and 2018. Samples were selected from patients who were referred to Avicenna RPL clinic with a history of at least two previously happened early unexplained miscarriages. The eligibility was defined strictly to select unexplained RPL patients homogenously. One hundred and seventy-three patients who got pregnant recently were allocated randomly into two groups LMWH plus low-dose aspirin treatment (Group A = 85) and low-dose aspirin treatment only (Group B = 88)) and were followed up till their pregnancy termination (delivery/abortion). A per-protocol analysis was carried out and all statistical tests were two-sided with a P < 0.05 significance level. Results: The live birth rates (LBRs) in Groups A and B were 78% and 77.1%, respectively, which did not show any statistically significant difference between the two groups, neither in rates nor in time of abortion. In subgroup analysis for polycystic ovary syndrome (PCOS) patients, the odds ratio for study outcome (intervention/control) was 2.25 (95% confidence interval: 0.65-7.73). There was no major adverse event whereas minor bleeding was observed in 18% of patients in Group A. Conclusion: LMWH does not improve the LBR in unexplained RPL patients, however, it is recommended to evaluate its effect separately in PCOS patients.

Comparison of Triggering Final Oocyte Maturation with Follicle Stimulating Hormone Plus Human Chorionic Gonadotropin, versus Human Chorionic Gonadotropin Alonein Normoresponder Women Undergoing Intracytoplasmic Sperm Injection: A Randomized Clinical Trial.

BACKGROUND: Few studies have so far been done about the role of follicle stimulating hormone (FSH) in final oocyte
maturation. However, none of these studies have been performed solely on normoresponder patients. This study aimed
to determine whether oocyte maturation, as well as fertilization and pregnancy rates, could be improved in normoresponder women with concomitant FSH and human chorionic gonadotropin (hCG) trigger compared to those with the hCG trigger alone.
Materials and Methods: In this prospective randomized clinical trial, 117 normoresponder women, aged 19-40 years
who were candidates for the gonadotropin-releasing hormone (GnRH) antagonist protocol at Avicenna Infertility
treatment Center, were enrolled and claasified in two groups. Final oocyte maturation was triggered using 10000 IU of
hCG plus 450 IU of FSH in the first group (59 subjects) and 10000 IU of hCG alone in the second group (58 subjects).
The primary outcome was clinical pregnancy rate.
Results: Mean age of the patients was 33.21 ± 4.41 years. There was no difference in clinical pregnancy among the
two groups (30.9% vs. 25.5%, P=0.525). There was no statistically significant difference in fertilization rate (80.0%
vs. 74.1%, P=0.106), implantation rates (18.9% vs. 16.7%, P=0.352), and chemical pregnancy rates (38.2% vs. 32.7%,
P=0.550). Oocyte maturation rate (84.2% vs. 73.6%, P<0.001), 2 pronuclei (2PNs) (6.53 ± 2.54 vs. 5.36 ± 2.85,
P=0.021) and total embryos (5.85 ± 2.43 vs. 4.91 ± 2.58, P=0.046) were significantly higher in the first group.
Conclusion: Adding FSH to hCG for oocyte triggering, significantly improved oocyte maturation rates and total embryos.
While there was no significant difference in the clinical and chemical pregnancy rates, between these two groups
(registration number: IRCT20190108042285N1).

Detection and Evaluation of Macrolide Resistance (Erythromycin) in Mycoplasma hominis Isolated from Endocervical Specimens of Patients Referring to Ibn Sina Infertility Treatment Centre, Tehran, Iran.

Background: Mycoplasma hominis (M. hominis) is an important cause of bacterial infections of the genital tract. Macrolides are the first selective agents used to treat mycoplasma infections. However, widespread use of macrolides has led to a rapid and global emergence of macrolide-resistant strains. We evaluated macrolide resistance in M. hominis isolated from endocervical specimens of patients who referred to Ibn Sina Infertility Centre in Tehran, Iran. Materials and Methods: In this cross-sectional descriptive-analytical study, 160 samples of Dacron endocervix swabs (80 infertile patient samples and 80 healthy controls) were collected and transferred to the laboratory. All samples were cultured in liquid pleuropneumonia-like organisms (PPLO) broth and PPLO agar solid media. After culturing and genome extraction, polymerase chain reaction (PCR) was performed using specific primers. Then, minimum inhibitory concentration (MIC) was obtained using the broth microdilution method. The MIC was recorded and reported for all samples positive for M. hominis against erythromycin. Results: From the 160 endocervical specimens cultured in PPLO agar medium, 19 cases (23.75%) were positive. A total of 35 cases (42.5%) were positive using specific primers of M. hominis species. MIC results from all samples positive for M. hominis were measured against erythromycin. All of the M. hominis samples were resistant to erythromycin. Conclusion: The results of the present study showed that a significant percentage of infertile women were infected with M. hominis. Also, MIC results from the broth microdilution method indicated that all strains positive for M. hominis were also resistant to erythromycin.

Association of leptin G2548A and leptin receptor Q223R polymorphisms and their serum levels with infertility and recurrent pregnancy loss in Iranian women with polycystic ovary syndrome.

BACKGROUND: Adipokine leptin plays a crucial role in metabolic and reproductive functions. Leptin receptor has a soluble form that binds to leptin, thus modulating its level in the circulation. It has been indicated that the levels of leptin and leptin receptor and also LEP rs7799039 and LEPR rs1137101 polymorphisms are associated with metabolic disorders. In the present study, we assessed the levels of leptin and soluble leptin receptor (sOB-R), and also the frequency of rs7799039 and rs1137101 polymorphisms in healthy fertile women and patients with polycystic ovary syndrome (PCOS), inclusive of PCOS-infertile and PCOS-recurrent pregnancy loss (RPL) subjects. METHODS: A total of 324 PCOS patients- including 199 infertile cases and 125 patients with a history of RPL- and 144 healthy controls were enrolled in this study. Biochemical parameters and plasma leptin and sOB-R levels were measured by ELISA and the genotypes of rs7799039 and rs1137101 polymorphisms were determined using PCR- RFLP. RESULTS: Plasma leptin and sOB-R levels were significantly higher and lower in PCOS, PCOS-infertile and PCOS RPL groups, respectively. The GG genotype frequencies of rs7799039 and rs1137101 polymorphisms were significantly different between PCOS-infertile women and non-PCOS subjects (P = 0.043, OR = 0.47, 95% CI = 0.22-0.97, and P = 0.01, OR = 0.31, 95% CI = 0.12-0.75, respectively). Increased LEP levels were associated with the risk of PCOS and RPL in women with PCOS (P = 0.039, OR = 1.203, 95%CI = [1.009-1.435] and P = 0.012, OR = 1.267, 95% CI = [1.054-1.522], respectively). CONCLUSION: Polymorphisms rs7799039 and rs1137101 and circulating leptin and sOB-R levels were associated with infertility in Iranian women with PCOS. Further studies are needed to reveal the role of leptin in PCOS pathogenesis.

Evaluation of angiopoietin-like protein 3 (ANGPTL3) levels in polycystic ovary syndrome.

AIM: Angiopoietin-like protein 3 (ANGPTL3) is recognized as a regulator of lipid metabolism. However, little is known about its association with insulin resistance in polycystic ovary syndrome (PCOS) setting. The present study aimed to investigate the serum levels of ANGPTL3 and adiponectin in PCOS women compared to healthy controls. MAIN METHOD: In this study, a total of 175 premenopausal women (117 PCOS and 58 non-PCOS) were enrolled. Serum concentrations of ANGPTL3, adiponectin, fasting insulin, and other hormonal variables were measured using ELISA technique. KEY FINDINGS: Results showed that adiponectin levels were significantly lower in PCOS group than those of non-PCOS group. However, serum levels of ANGPTL3, high-sensitivity C-reactive protein (hs-CRP), and homocysteine (Hcy) were found to be higher in PCOS patients, when compared to non-PCOS ones. Moreover, serum ANGPTL3 positively correlated with BMI and serum triglyceride, while it inversely correlated with serum HDL-C in PCOS patients. SIGNIFICANCE: Our results demonstrated that increased levels of ANGPTL3 correlated with insulin resistance and dyslipidemia in PCOS patients, highlighting the need for future studies targeting its role in the pathogenesis of this disease.

Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study.

Patients diagnosed with polycystic ovary syndrome (PCOS) are at high risk of developing a myriad of endocrinologic and metabolic derailments. Moreover, PCOS is a leading cause of habitual abortion, also known as recurrent pregnancy loss (RPL). Meteorin-like protein (Metrnl) is a newly discovered adipokine with the potential to counteract the metaflammation. This study aimed at determining the associations of serum Metrnl levels with homocysteine, hs-CRP, and some components of metabolic syndrome in PCOS-RPL and infertile PCOS patients.This case-control study was conducted in 120 PCOS patients (60 PCOS-RPL and 60 infertile) and 60 control. Serum hs-CRP and homocysteine were assessed using commercial kits, while adiponectin, Metrnl, FSH, LH, free testosterone and insulin levels were analyzed using ELISA technique. Serum Metrnl levels were found to be lower in PCOS patients when compared to controls (67.98 ± 26.66 vs. 96.47 ± 28.72 pg/mL, P <0.001)). Furthermore, serum adiponectin levels were lower, while free testosterone, fasting insulin, HOMA-IR, homocysteine, and hs-CRP were significantly higher in PCOS group compared to controls. Moreover, serum Metrnl correlated with BMI, adiponectin, and homocysteine in controls, and inversely correlated with FBG, fasting insulin, and HOMA-IR in PCOS group and subgroups. Besides, it inversely correlated with hs-CRP in control, and PCOS group and subgroups. These findings revealed a possible role of Metrnl in the pathogenesis of PCOS and RPL. Nevertheless, there is a necessity for future studies to prove this concept.

Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor-α-related protein-6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf-PCOS] and PCOS-RPL). This case-control study included 120 PCOS patients (60 inf-PCOS and 60 PCOS-RPL) and 60 healthy controls. Serum high-sensitivity C-reactive protein (hs-CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf-PCOS and PCOS-RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs-CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs-CRP in PCOS group and inf-PCOS subgroup, but not PCOS-RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.

Efficacy of Intrauterine Injection of Granulocyte Colony Stimulating Factor (G-CSF) on Treatment of Unexplained Recurrent Miscarriage: A Pilot RCT Study.

BACKGROUND: Endometrium undergoes several changes in structure and cellular composition during pregnancy. Granulocyte Colony-stimulating Factor (GCS-F) is an important cytokine with critical role in embryo implantation and pregnancy. The aim of the present study was to evaluate the impact of intrauterine injection of G-CSF in patients who suffer from unexplained recurrent miscarriage (RM). METHODS: In the present randomized clinical trial, a total of 68 patients were randomly allocated into two study groups including intrauterine G-CSF (n=23, 300 µg) injection and control group (n=27, no G-CSF injection). Eighteen out of 68 patients were excluded from the final analysis due to different reasons. All patients were in Ovulation Induction (I/O) cycle. In G-CSF group, intrauterine injection of G-CSF was done twice in the cycle. All enrolled patients were under 40 years old and had at least two unexplained pregnancy losses. Pregnancy was evaluated by titer of ßhCG, presence of gestational sac (implantation) and fetal heart rate (clinical pregnancy) was assessed by vaginal ultrasonography. Student's T test and Mann-Whitney U were used for analysis. The p≤0.05 was determined as statistically significant. RESULTS: No significant differences were observed between the two study groups when the rates of chemical pregnancy (26.1% vs. 29.6%, p=0.781), implantation (26.1% vs. 22.2%, p=0.750), clinical pregnancy (17.4% vs. 11.1%, p=0.689) and abortion (33% vs. 37.5%, p=0.296) were compared. CONCLUSION: In our study, no significant difference was observed between the two study groups when the rates of chemical pregnancy, implantation, clinical pregnancy and abortion were compared.