Adding L-carnitine to antagonist ovarian stimulation doesn't improve the outcomes of IVF/ ICSI cycle in patients with polycystic ovarian syndrome: a double-blind randomized clinical trial.

OBJECTIVE: To investigate the effect of L-carnitine supplementation during the controlled ovarian stimulation (COS) cycle with antagonist protocol in patients with polycystic ovary syndrome (PCOS) diagnosis undergoing IVF/ICSI treatment. METHODS AND MATERIALS: This was a double-blind clinical trial study including 110 patients with PCOS attended to Royan Institute between March 2020 and February 2023. At the beginning of the COS cycle, the eligible patients were allocated into two groups randomly according to the coding list of the drugs prepared by the statistical consultant. In the experimental group, patients received 3 tablets daily (L-carnitine 1000 mg) from the second day of menstruation of the previous cycle until the puncture day in the cases of freeze-all embryos (6 weeks) or until the day of the pregnancy test (8 weeks) in fresh embryo transfer cycle. In the control group, patients received 3 placebo tablets for the same period of time. Weight assessment and fasting blood sugar and insulin tests, as well as serum lipid profile were also measured at the baseline and ovum pick-up day. The results of the COS cycle as well as the implantation and pregnancy rates were compared between groups. RESULTS: Finally, 45 cases in L-carnitine group versus 47 cases in the placebo group were completed study per protocol. Data analysis showed that the two groups were homogeneous in terms of demographic characteristics and baseline laboratory tests and severity of PCOS. There is no statistically significant difference in terms of the oocyte recovery ratio and oocyte maturity rate, and the number and quality of embryos, as well as the rates of the fertilization, chemical and clinical pregnancy between groups. However, the means of weight (P < 0.001) and serum levels of fasting blood sugar (P = 0.021), fasting insulin (P = 0.004), triglyceride (P < 0.001) and cholesterol (P < 0.001), LDL (P < 0.001) have significantly decreased in women after consuming L-carnitine supplementation. CONCLUSION: The oral intake of L-carnitine during COS in PCOS women for 6 weeks had no effect on COS and pregnancy outcomes. However, taking this supplement for 6 weeks has been associated with weight loss and improved lipid profile and serum glucose. TRIAL REGISTRATION: The study was registered in the Clinicaltrials.gov site on December 17, 2020 (NCT04672720).

The Predictive Value of Serum ß-HCG Levels in The Detection of Ectopic Pregnancy Sixteen Days after Embryo Transfer: A Cross-Sectional Study.

BACKGROUND: To detect the predictive value of beta human chorionic gonadotropin (ß-hCG) levels 16 days post embryo transfer (ET) regarding detection of an ectopic pregnancy (EP) in assisted reproductive technology (ART) cycles. MATERIALS AND METHODS: In this cross-sectional study, we reviewed the database of Royan Institute from January 2011 to December 2014 and from January 2017 to December 2019 retrospectively. All cases with positive ß-hCG levels sixteen days after ET were screened (n=4149). The pregnancies with oocyte or embryo donation and the multiple pregnancies based on the first ultrasound were excluded. All eligible singleton pregnancies with documented serum ß-hCG levels at Royan institute laboratory (n=765) were included and then classified according to the type of pregnancy: EP (n=189) or non-EP (n=576). The data of the treatment cycle was extracted from the patients' files. A receiver operating characteristic (ROC) curve was used to detect the predictive power of the first measurement of ß-hCG level in distinguishing EP from ongoing pregnancy in the ART and intrauterine insemination (IUI) cycles separately. Sensitivity, specificity, area under the ROC curve and 95% confidence intervals (CI) were calculated for each of the estimates. RESULTS: The mean levels of ß-hCG 16 days after ET were remarkably higher in the ongoing pregnancy group than the EP group (1592.35 ± 87 IU/L vs. 369.69 ± 50.61 IU/L, P<0.001). The ß-hCG thresholds predictive of ongoing pregnancy were 278 IU/L as the most suitable cut-off to predict viable pregnancy with a sensitivity of 72.8%, a specificity of 67.5%, a positive predictive value of 77.8%, standard error of 0.02, and a confidence interval of 73.8- 81.7%. However, this relationship was not found in IUI cycles. CONCLUSION: Based on these findings, if ß-hCG levels 16 days after ET are below 278 IU/l, close follow-up is recommended, until either the diagnosis of EP or miscarriage is established.

Birth prevalence of genital anomalies among males conceived by intracytoplasmic sperm injection cycles: A cross-sectional study.

Background: Several studies have been conducted worldwide to evaluate the prevalence and relative risks of congenital anomalies associated with assisted reproductive technology cycles; however, there is limited data in Iran. Objective: To investigate male genital anomalies among live births from assisted reproductive technology. Materials and Methods: This cross-sectional study was conducted on children born after intracytoplasmic sperm injection (ICSI) at Royan Institute, Tehran, Iran from April 2013-December 2015. The prevalence of male genitalia disorders that included hypospadias, epispadias, cryptorchidism, micropenis, and vanishing testis were reported. The relationship between the cause of infertility and type of embryo transfer (fresh or frozen), gestational age at birth (term or preterm), and birth weight with these male genitalia anomalies were evaluated. Results: In total, 4409 pregnant women were followed after their ICSI cycles to evaluate genitalia anomalies in their children. Out of 5608 live births, 2614 (46.61%) newborns were male, of which 14 cases (0.54%) had genital anomalies. The prevalence of various anomalies were cryptorchidism (0.34%), hypospadias (0.038%), micropenis (0.038%), vanishing testis (0.038%), and epispadias (0.077%). No relationship was found between the cause of infertility, type of embryo transfer (fresh or frozen), gestational age at birth (term or preterm), and male genital malformation (p = 0.33, p = 0.66, and p = 0.62, respectively). Conclusion: The prevalence of each male genital anomaly after the ICSI cycle was rare and less than 0.5%; however, no significant infertility-related factor was observed with these anomalies.

The effect of metabolic syndrome on controlled ovarian stimulation outcome in infertile women with polycystic ovary syndrome undergoing assisted reproductive technology cycles

ABSTRACT Objective: To evaluate the effect of metabolic syndrome (MetS) diagnosis on oocyte quality and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS) who undergoing antagonist-controlled ovarian stimulation (COS) and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Subject and methods: This prospective cohort study was conducted from November 2019 to November 2020 across two university-affiliated infertility centers in Iran. The PCOS diagnosis was defined according to the Rotterdam criteria. The patients prior to IVF/ICSI cycles were evaluated for MetS diagnosis. MetS was detected according to the National Cholesterol Education Program/Adult Treatment Panel III with the presence of at least three or more of the specific clinical criteria. The cycle outcomes were compared between MetS and non-MetS groups. Results: Overall, 68 eligible infertile PCOS patients with MetS diagnosis and 126 without MetS participated. The MetS diagnosis was associated with the increased requirement of gonadotropins and the COS duration significantly (P = 0.001). Although the total numbers of retrieved and MII oocytes, obtained and top-quality embryos as well as clinical pregnancy and live birth rates in the MetS group were lower than those of in the non-MetS group, the differences were not statistically significant (P > 0.05). In follow-up of the obstetrics complications, the rate of preeclampsia was significantly higher in patients with MetS (P = 0.02). Conclusion: MetS diagnosis in PCOS patients was associated with non-significant poor COS and pregnancy outcome. Further studies with larger sample sizes are recommended to clarify the risk of MetS in patients undergoing ART cycles.

The effect of metabolic syndrome on controlled ovarian stimulation outcome in infertile women with polycystic ovary syndrome undergoing assisted reproductive technology cycles.

Objective: To evaluate the effect of metabolic syndrome (MetS) diagnosis on oocyte quality and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS) who undergoing antagonist-controlled ovarian stimulation (COS) and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods: This prospective cohort study was conducted from November 2019 to November 2020 across two university-affiliated infertility centers in Iran. The PCOS diagnosis was defined according to the Rotterdam criteria. The patients prior to IVF/ICSI cycles were evaluated for MetS diagnosis. MetS was detected according to the National Cholesterol Education Program/Adult Treatment Panel III with the presence of at least three or more of the specific clinical criteria. The cycle outcomes were compared between MetS and non-MetS groups. Results: Overall, 68 eligible infertile PCOS patients with MetS diagnosis and 126 without MetS participated. The MetS diagnosis was associated with the increased requirement of gonadotropins and the COS duration significantly (P = 0.001). Although the total numbers of retrieved and MII oocytes, obtained and topquality embryos as well as clinical pregnancy and live birth rates in the MetS group were lower than those of in the non-MetS group, the differences were not statistically significant (P > 0.05). In followup of the obstetrics complications, the rate of preeclampsia was significantly higher in patients with MetS (P = 0.02). Conclusion: MetS diagnosis in PCOS patients was associated with non-significant poor COS and pregnancy outcome. Further studies with larger sample sizes are recommended to clarify the risk of MetS in patients undergoing ART cycles.

The effect of laparoscopic ovarian drilling on pregnancy outcomes in polycystic ovary syndrome women with more than 2 in-vitro fertilization cycle failures: A pilot RCT.

Background: The effect of laparoscopic ovarian drilling (LOD) before in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles on pregnancy outcomes is an unclear and challenging subject. Objective: To evaluate the impact of LOD before IVF/ICSI cycles on controlled ovarian stimulation and pregnancy outcomes in polycystic ovary syndrome (PCOS) women with a history of more than 2 IVF failures. Materials and Methods: In this randomized clinical trial, women with PCOS diagnosis who referred to Arash Women's hospital, Tehran, Iran for IVF/ICSI cycle from August 2015-January 2018 were evaluated. Eligible participants were allocated into 2 groups randomly (n = 17/each group). The participants in the LOD group (intervention) were treated with laparoscopic couture, and after one month, they underwent IVF/ICSI cycles using the gonadotropin-releasing hormone antagonist protocol. The control group had no intervention. The oocyte and embryo qualities, ovarian hyperstimulation syndrome rate, the rates of chemical and clinical pregnancy and early miscarriage, live birth, and pregnancy complications, were compared between groups. Results: Finally, 34 participants were evaluated. The controlled ovarian stimulation outcomes were similar between groups. The ovarian hyperstimulation syndrome rate in the LOD group was significantly lower than in the control group (p = 0.04). One case of spontaneous pregnancy was reported in the LOD group. No significant difference was observed between groups in clinical pregnancy, miscarriage, and live birth rates. The rates of pregnancy complications (gestational diabetes mellitus, preeclampsia, and preterm birth) were similar between groups. Conclusion: Performing LOD before IVF/ICSI cycles did not improve the pregnancy outcomes in PCOS women, a clinical trial with a larger sample size is needed to prove these results.

Early Postpartum Glucose Intolerance, Metabolic Syndrome and Gestational Diabetes Mellitus Determinants after Assisted Conception: A Prospective Cohort Study.

BACKGROUND: This study aimed to determine the prevalence of postpartum metabolic syndrome (MetS), glucose intolerance,
and the determinants, 6-12 weeks postpartum in women with assisted reproduction technology conception
gestational diabetes mellitus diagnosis (ART-GDM) compared to women with spontaneous conception and GDM
diagnosis (SC-GDM).
Materials and Methods: In this prospective cohort study, two groups consisting of 62 ART-GDM and 64 SC-GDM
singleton pregnant women were followed 6-12 weeks after delivery for postpartum MetS. Fasting glucose, 75-g 2-h
OGTT, and lipid profile were assessed. Waist and hip circumference, and systolic and diastolic blood pressures (BP)
were measured at postpartum. Clinical, paraclinical, and obstetric data were recorded from registry offices. The prevalence
of MetS and glucose intolerance were determined. Predictors of MetS and glucose intolerance were evaluated
by logistic regression.
Results: The prevalence of postpartum MetS was 20.8% in ART-GDM women and 10.9% in SC-GDM (P=0.123).
Mean postpartum BMI and systolic BP were significantly higher in the ART-GDM group (P=0.016 and P=0.027
respectively). Adverse pregnancy outcomes were significantly higher in the ART-GDM group. Postpartum glucose
intolerance prevalence did not vary significantly between the groups. Family history of diabetes was a predictive factor
for postpartum MetS and glucose intolerance 6-12 weeks after delivery.
Conclusion: Early postpartum MetS and glucose intolerance prevalence after assisted conception did not vary significantly;
however, postpartum body mass index (BMI) and systolic BP were significantly higher in the ART-GDM group.
Lifestyle modification programs and long-term health care of ART women with GDM diagnosis can be recommended.
Further studies with larger sample size and longer follow-up are necessary to verify our findings.

Live birth rates in different subgroups of poor ovarian responders according to Bologna and POSEIDON group classification criteria.

PURPOSE: The present study was designed to compare the live birth rates (LBRs) according to Bologna criteria or Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) group classifications to determine the important predictive factors for LBR in patients with POR. BASIC PROCEDURES: In this cross-sectional study, the database of Royan Institute (Tehran, Iran) from December 2015 to December 2017 was evaluated and the fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles outcomes for all the patients with at least one POR after standard controlled ovarian stimulation were collected. The patients divided into five subgroups according to Bologna criteria and four groups on the basis of POSEIDON group classification. MAIN FINDING: 812 patients with POR diagnosis were assessed which 517 (63.6%) of them were underwent embryo transfer (ET) during the last treatment cycle. According to Bologna criteria, 41 patients were not included in any subgroup and the patients in Bologna group II had highest LBR (19.8%). In terms of POSEIDON classification, all of the patients were classified into subgroups and the women in POSEIDON group III had the highest LBR (27%). According to multivariable regression analysis, the significant independent predictive factors for LBR were the number and morphology (good and excellent) of the embryos transferred, and POSEIDON group III classification. PRINCIPAL CONCLUSION: The results indicated that the POSEIDON group classification could be more comprehensive and practical than Bologna criteria for categorizing POR patients and predicting their outcome. Moreover, the number and morphology of transferred embryos were the most important prognostic factors for live births in these patients.

Assisted conception as a potential prognostic factor predicting insulin therapy in pregnancies complicated by gestational diabetes mellitus.

BACKGROUND: Advanced maternal age, family history of diabetes, pre-gestational obesity, increased level of HbA1c, history of gestational diabetes mellitus (GDM), and poor pregnancy consequences are considered risk factors for antenatal insulin requirement in women with GDM. However, the role of assisted reproductive technology (ART) in increasing the risk of insulin therapy in pregnancies complicated with GDM remained elusive. The current study aimed to determine the role of ART in predicting insulin therapy in GDM women and investigate the clinical and biochemical factors predicting the need for insulin therapy in pregnancies complicated with GDM. METHODS: In this prospective cohort study, 236 Iranian women with GDM were diagnosed by one-step oral glucose tolerance test (OGTT) between October 2014 and June 2017. They were mainly assigned to two groups; the first group (n = 100) was designated as ART which was further subdivided into two subgroups as follows: 60 participants who received medical nutrition therapy (MNT) and 40 participants who received MNT plus insulin therapy (MNT-IT). The second group (n = 136) was labeled as the spontaneous conception (SC), consisting of 102 participants receiving MNT and 34 participants receiving MNT in combination with IT (MNT-IT). The demographic, clinical, and biochemical data were compared between groups. Multivariate logistic regression was performed to estimate prognostic factors for insulin therapy. RESULTS: A higher rate of insulin therapy was observed in the ART group as compared with the SC group (40% vs. 25%; P < 0.001). Multivariate logistic regression demonstrated that maternal age ≥ 35 years [OR: 2.91, 95% CI: (1.28-6.62)], high serum FBS [1.10: (1.04-1.16)], HbA1c [1.91 (1.09-3.34)], and ART treatment [2.94: (1.24-6.96)] were independent risk factors for insulin therapy in GDM women. CONCLUSIONS: Apart from risk factors mentioned earlier, ART may be a possible prognostic factor for insulin therapy in pregnancies complicated with GDM.

Serum estradiol level on trigger day impacts clinical pregnancy rate in modified natural frozen embryo transfer cycles.

OBJECTIVE: To examine the predictive value of serum estradiol and progesterone on the day of human chorionic gonadotropin (hCG) administration and embryo transfer for clinical pregnancy rate in modified natural-cycle frozen embryo transfer (NC-FET). METHODS: In a longitudinal prospective study, all eligible women who underwent NC-FET cycles with hCG triggering in Royan Institute, Tehran, Iran, from June 1, 2015, to December 31, 2016, were evaluated. Serum estradiol and progesterone levels were measured at menstrual cycle initiation, on day of trigger with hCG, on day of embryo transfer, and in pregnant women every 7 days until the observation of a gestational sac with embryonic heartbeat. RESULTS: In total, 101 modified natural FET cycles were assessed, and the clinical pregnancy and live birth rates achieved were 34 (33.6%) and 32 (31.6%), respectively. The changes in estradiol level during early pregnancy showed an increase by an average of 200 pg/mL per week. Multivariable logistic regression analysis showed that only the estradiol level on the hCG day was a significant predictive variable for clinical pregnancy following NC-FET (P=0.04). CONCLUSION: Estradiol level on the day of hCG trigger predicted the clinical pregnancy rates after modified NC-FET; this likely mirrored the developmental competence of the corpus luteum and an appropriate luteal structure-function.

The Effects of Maternal and Paternal Body Mass Index on Live Birth Rate after Intracytoplasmic Sperm Injection Cycles.

BACKGROUND: We designed the present study to evaluate the simultaneous effect of obesity in couples on in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) outcomes. MATERIALS AND METHODS: In this cross-sectional study, performed at Royan Institute between January 2013 and January 2014, we evaluated the recorded data of all patients during this time period. The study population was limited to couples who underwent ICSI or IVF/ICSI cycles with autologous oocytes and fresh embryo transfers. We recorded the heights and weights of both genders and divided them into groups according to body mass index (BMI). Multilevel logistic regression analysis was used to determine the odds ratio for live births following ICSI or IVF/ICSI. RESULTS: In total, 990 couples underwent IVF/ICSI cycles during the study period. Among the ovulatory women, a significant difference existed between the BMI groups. There was a 60% decrease [95% confidence interval (CI): 0.11-0.83] in the odds of a live birth among overweight subjects and 84% (95% CI: 0.02-0.99) decrease among obese subjects. Among the anovulatory women, the association between the BMI and live births presented no clear tendencies. We did not observe any significant relationship between male BMI and live birth rate. The results demonstrated no significant association between the couples' BMI and live birth rate. CONCLUSION: Based on the present findings, increased female BMI independently and negatively influenced birth rates after ICSI. However, increased male BMI had no impact on live births after ICSI, either alone or combined with increased female BMI.

Diagnostic Accuracy of Body Mass Index and Fasting Glucose for The Prediction of Gestational Diabetes Mellitus after Assisted Reproductive Technology.

BACKGROUND: The aim of the present study was to determine the maternal pre-pregnancy body mass index (BMI), first-trimester fasting blood sugar (FBS), and the combination of (BMI+FBS) cut-points for at-risk pregnant women conceived by assisted reproductive technology (ART) to better predict the risk of developing gestational diabetes mellitus (GDM) in infertile women. MATERIALS AND METHODS: In this nested case-control study, 270 singleton pregnant women consisted of 135 (GDM) and 135 (non-GDM) who conceived using ART were assessed. The diagnosis of GDM was confirmed by a one-step glucose tolerance test (O-GTT) using 75 g oral glucose. BMI was classified base on World Health Organization (WHO) criteria. The relationship between BMI, FBS, and BMI+FBS with the risk of GDM development was determined by logistic regression and adjusted for confounding factors. Receiver operating characteristic (ROC) curve analysis was performed to assess the value of BMI, FBS, and BMI+FBS for the prediction of GDM. RESULTS: The GDM group had significantly higher age, BMI, family history of diabetes, and history of polycystic ovary syndrome in comparison with the non-GDM group (P<0.05). Overweight and obese women had 3.27, and 5.14 folds increase in the odds of developing GDM, respectively. There was a 17% increase in the risk of developing GDM with each 1 mg/dl increase in fasting glucose level. The cut points for FBS 84.5 mg/dl (72.9% sensitivity, 74.4% specificity), BMI 25.4 kg/m2 (68.9% sensitivity, 62.8% specificity), and BMI+FBS 111.2 (70.7% sensitivity, 80.6% specificity) was determined. CONCLUSION: The early screening and high-quality prenatal care should be recommended upon the co-occurrence of high FBS (≥84.5 mg/dl) in the first-trimester of the pregnancy and the BMI (≥25.4 kg/m2) in pre-pregnancy period in women undergone ART. The combination of BMI and FBS is considered a better prediction value.

The incidence rate of unresponsive thin endometrium in frozen embryo transfer cycles: A case-series of therapy with granulocyte colony stimulating factor.

BACKGROUND: Treatment-resistant thin endometrium (TTE) during in-vitro fertilization is a relatively uncommon and challenging problem. OBJECTIVE: The primary aim of the study was to assess the TTE rate during frozen embryo transfer (FET) cycles and the secondary aim was to evaluate the effect of intrauterine instillation of granulocyte colony stimulating factor (G-CSF) in these cases. MATERIALS AND METHODS: In this cross-sectional study, all of the women who underwent FET cycles with hormonal endometrial preparation in Royan Institute from June 2015 to March 2018 were evaluated and all of the cases with TTE diagnosis (endometrial thickness < 7 mm after using high doses of estradiol) were included. In the eligible cases, 300 µgr of G-CSF was infused intrauterine. If the endometrium had not reached at least a 7-mm, a second infusion was prescribed within 48 hr later. RESULTS: During the study, 8,363 of FET cycles were evaluated and a total of 30 infertile patients (0.35%) with TTE diagnosis were detected. Finally, 20 eligible patients were included. The changes of endometrial thickness after G-CSF therapy were significant (p < 0.001); however, the endometrial thickness did not reach 7 mm in nine patients (45%) and the embryo transfer was canceled. CONCLUSION: It was found that the rate of TTE during the FET cycle is very low and intrauterine perfusion of G-CSF has a potential effect to increase the endometrial thickness in these patients; however, the rate of cancellation was still high and poor pregnancy outcomes were observed.

The impact of the localisation of endometriosis lesions on ovarian reserve and assisted reproduction techniques outcomes.

This case-control study was designed to evaluate the impact of endometriosis and the presence of endometrioma (OMA) per se on the serum anti-Müllerian hormone (AMH) level and also to compare the in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes after therapeutic surgery in endometriosis patients, according to the localisation of endometriosis lesions. One hundred and fifty two infertile women ≤40 years with suspicious symptoms were surgically evaluated to detect the aetiology of infertility at the Royan Institute during this study and, in parallel, 131 patients with a male factor infertility diagnosis were considered as the control group. The serum AMH level and IVF/ICSI outcomes were compared according to the nature and extension degree of endometriosis lesions. The results demonstrated that the existence of a deep infiltrating endometriosis (DIE) with and without OMA was associated with a significant decrease in AMH level, antral follicle count and ovarian sensitivity index (OSI) (p < .001 and p = .007, respectively). The multivariable logistic regression analysis adjusted for confounding factors indicated that the OSI and the existence of DIE with and without OMA were a significant predictive variable for clinical pregnancy and for live birth. On the basis of our results, the severity of endometriosis and the location of its lesions could affect an ovarian reserve and the ovarian stimulation outcomes. Impact Statement What is already known on this subject? Previous studies have evaluated the impact of endometrioma (OMA) on ovarian reserve and the assisted reproduction technology (ART) outcomes and controversial results have been reported; therefore, it seems that this topic still needs further research. What the results of this study add? In the present study, the effect of endometriosis lesions' localisation on ovarian reserve and the success rate of the in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle after therapeutic surgery were compared with that of the control group. It was found that the existence of a deep infiltrating endometriosis (DIE) with and without OMA was associated with a significant decrease in the anti-Müllerian hormone (AMH) level, antral follicle count, ovarian sensitivity index (OSI), clinical pregnancy and live birth rates. What the implications are of these findings for clinical practice and/or further research? The results of this study has a practical value in the decision making process for the ovarian stimulation protocol in patients with the different severity of endometriosis and the counselling regarding the success rate of IVF or ICSI/embryo transfer cycles.

The effect of weight loss program on serum anti-Müllerian hormone level in obese and overweight infertile women with polycystic ovary syndrome.

We evaluated the predictive value of serum anti-Müllerian hormone (AMH) levels for improved menstrual cycles in response to dietary management in women with polycystic ovary syndrome (PCOS). In addition, we assessed the effect of a restricted calorie diet for 12 weeks on serum AMH levels. This intervention study was carried out at Rohan Institute, Tehran, Iran from 2013 to 2015. A total of 105 overweight and obese women with PCOS and reproductive impairment participated in a 12-week weight loss program (WLP). The serum AMH levels, weight, and menstrual cyclicity were assessed at baseline and post-intervention for all of the participants. A total of 90 patients completed the 12-week WLP. Of the 90 patients, 65 (72.2%) responded to the intervention with improvements in menstrual cyclicity. There were no significant differences in terms of age, baseline AMH levels, and other hormone profiles between responders and nonresponders. Responders had a significantly lower baseline body mass index (BMI) and waist circumference compared with nonresponders. These factors were the clinical predictors for a menstrual response after the intervention. The AMH levels did not significantly change after 12-week WLP despite the overall reduced weight; however, women who responded with improved reproductive function had a greater reduction in AMH levels.

Does the "delayed start" protocol with gonadotropin-releasing hormone antagonist improve the pregnancy outcome in Bologna poor responders? a randomized clinical trial.

BACKGROUND: Recently, a novel approach with delaying the start of controlled ovarian stimulation along with gonadotropin-releasing hormone (GnRH) antagonist pretreatment for 7 days after estrogen priming for further suppression of endogenous follicle stimulating hormone (FSH) during the early follicular phase, resulting in more FSH-responsive follicles and thus improving synchronous follicular development was introduced. Two clinical trials have examined this strategy and reported controversial results. This study aimed to compare the effect of delayed-start GnRH antagonist protocol and standard GnRH antagonist in patients with poor ovarian response (POR) undergoing in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI). METHODS: This randomized clinical trial was conducted at infertility department of Royan Institute from January 2017 to June 2018. Poor ovarian response was defined according to the Bologna criteria. The eligible women were randomly allocated into an experimental and control groups. In experimental group, patients received delayed-start GnRH antagonist protocol with estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin and in control group, patients treated with estrogen priming antagonist protocol. IVF/ICSI outcomes were compared between groups. RESULTS: Among all the 250 patients examined 156 women were eligible for study and finally 120 patients were allocated to intervention (n = 60) and control (n = 60) groups. Demographic characteristics and hormonal profiles of the patients did not differ between groups. The statistical analysis showed that there were significant differences between groups regarding the total dose of used gonadotropins (P < 0.001), stimulation duration (P < 0.001), number of retrieved oocytes (P = 0.01) and top quality embryo (P < 0.001) and also cancellation (P = 0.002) and fertilization rates (P = 0.002). CONCLUSION: On the basis of present results the delayed-start protocol in poor responders can improve the fertilization rate and quality of embryos and reduce the cycle cancellation but have no significant effect on clinical pregnancy rate; however, larger randomized clinical trials are required to compare it with other protocols. TRIAL REGISTRATION: NCT, NCT03134690. Registered 1 May 2017 - Retrospectively registered, http://www.clinicaltrial.gov / NCT03134690.

Obstetric and perinatal outcomes of singleton pregnancies conceived via assisted reproductive technology complicated by gestational diabetes mellitus: a prospective cohort study.

BACKGROUND: Growing evidence indicates that the risk of obstetric and perinatal outcomes is higher in women with assisted reproductive technology (ART). However, there is little known about pregnancy related complications and co-morbidity in gestational diabetes mellitus (GDM) following singleton pregnancies achieved by ART in comparison with spontaneous conception (SC). METHODS: Two hundred sixty singleton pregnant women conceived by ART and 314 pregnant women conceived by spontaneous conception (SC) were participated in this prospective cohort study. All participants were enrolled after GDM screening through one-step oral glucose tolerance test (OGTT) and then grouped into GDM and non-GDM groups. Women were followed for pregnancy outcomes including pregnancy-induced hypertension (PIH), preeclampsia, antepartum hemorrhage (APH), cesarean section (CS), preterm birth (PTB), intrauterine growth restriction (IUGR), being small or large for gestational age (SGA or LGA), macrosomia, low birth weight (LBW), respiratory distress, neonatal hypoglycemia, NICU admission and perinatal mortality from antenatal visits to delivery. Confounding factors were adjusted in logistic regression model in order to estimate adjusted odds ratios (aORs). RESULTS: Among 260 ART and 314 SC, 135 and 152 women were GDM women, respectively. Higher maternal age and pre-gravid BMI, shorter duration of gestation and lower gestational weight gain were observed in GDM groups (ART-GDM and SC-GDM) compared to those of the SC group. ART-GDM group had a higher risk (95% confidence interval) of obstetric complications including PIH [aOR:7.04 (2.24-22.15)], preeclampsia [aOR:7.78 (1.62-37.47)], APH [aOR:3.46 (1.28-9.33)], emergency CS [aOR:2.64 (1.43-4.88)], and perinatal outcomes such as PTB [aOR:3.89 (1.51-10.10)], LBW [aOR:3.11 (1.04-9.30)] and NICU admission [aOR:4.36 (1.82-10.45)], as well as neonatal hypoglycemia [aOR: 4.91 (1.50-16.07)], compared to SC group. SC-GDM group showed a higher risk of PIH [aOR: 4.12 (1.31-12.89)], emergency CS [aOR: 2.01 (1.09-3.73] and LGA [aOR: 5.20 (1.07-25.20)], compared to SC group. Additionally, ART group had a higher risk of PIH [aOR: 3.46(1.02-11.68), preeclampsia 5.29 (1.03-27.09), and NICU admission [aOR: 2.53 (1.05-6.09)] compared to SC. Insulin requirement (41.8% vs. 25.7%) was significantly higher in ART-GDM group compared to SC-GDM group. CONCLUSION: The findings of this study suggest that GDM occurring after ART conception increases the risk of adverse obstetric and perinatal outcomes.

Predictive factors of gestational diabetes in pregnancies following assisted reproductive technology: a nested case-control study.

PURPOSE: To evaluate predictive factors for gestational diabetes mellitus (GDM) in singleton pregnancy following assisted reproductive technology (ART). METHODS: This nested case-control study was performed during October 2016-June 2017. Pregnant women who conceived following ART procedures referred to infertility clinic were selected and categorized into GDM and non-GDM based on ADA/IAPDSG criteria. The study variables including age, educational status, first-degree family history of chronic diseases, systolic and diastolic blood pressure, previous obstetric and perinatal outcomes, infertility history, and ART cycle characteristics were collected from medical records. Prediction model to develop GDM was employed by binary logistic regression analysis after adjustment for age and body mass index, family history of diabetes, and gravidity. RESULTS: In total, 270 women with singleton pregnancies (consisted of 135 GDM and 135 non-GDM women) conceived were studied. According to the final model, significant predictors of GDM were history of polycystic ovarian syndrome (PCOS), previous ovarian hyper-stimulation syndrome (OHSS) risk and progesterone injections. Administration of injectable progesterone during the first 10-12 weeks of pregnancy was associated with an approximately twofold increased risk of developing GDM [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.27-4.09)] compared to vaginal progesterone. In addition, the regression analysis revealed that previous OHSS risk (OR 2.40, 95% CI 1.34-4.31) and history of PCOS (OR 2.76, 95% CI 1.26-6.06) were other most important predictors of GDM. CONCLUSIONS: The route of progesterone administration, previous OHSS risk and history of PCOS seem to be putative risk factors for GDM in women conceived by ART.

The effects of superovulation with gonadotropins on autoantibody levels in patients undergoing assisted reproductive cycles.

PURPOSE: To evaluate the effect of controlled ovarian stimulation (COH) with gonadotropins on the serum levels of autoantibodies in the women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles and to compare basal levels of these autoantibodies between groups according to history of COH. METHODS: This prospective cohort study was performed from October 2014 to March 2016 in the Royan Institute. The volunteered infertile women with regard to the inclusion criteria, who underwent IVF/ICSI cycles, were recruited. The COH was performed according to standard long GnRH agonist protocol. The mean levels of the autoantibodies including anti-nuclear, anti-smooth muscle, anti-ovarian, anti-mitochondrial, anti ß2-glycoprotein I, anti-parietal cell and anti-follicle-stimulating hormone antibodies were measured at three time points: on the 3-5 days of the menstrual cycle, 1 week after starting of COH and the ovum pick-up (OPU) day. RESULTS: Of all participants (n = 189), 73 women had history of COH (group B) and 116 women did not have such history (group A). The analysis indicated that the autoantibodies changes during COH were similar in both groups. COH has no significant impact on the level of autoantibodies during the stimulation cycle. Multiple logistic regression analysis showed that the serum levels of anti-smooth muscle antibody on OPU day was the positive predictive factors for live birth following ART cycles in the studied population. CONCLUSION: No significant effect of COH on the studied autoantibodies by the time of OPU was found but further studies are required to interpret these results.