Extending the culture of cleavage-stage embryos to the blastocyst stage after warming increases the chance of live birth: does it have a regenerative effect?

PURPOSE: We aimed to evaluate the effect of extending the culture of cleavage-stage embryos to the blastocyst stage in vitrified-warmed cycles on pregnancy outcomes. METHODS: This is a retrospectively designed pilot study of a single center. All patients who applied for freeze-all cycle procedures during in vitro fertilization treatment were included in the study. Patients were classified into three subgroups. The embryos obtained were frozen at the cleavage or blastocyst stage. After a warming process, the cleavage-stage embryos were divided into two subgroups: the first group of embryos was transferred (vitrification day 3-embryo transfer (ET) day 3 (D3T3)) on the warming day; for the second group, the embryo culture was extended to the blastocyst stage (vitrification day 3-ET day 5 (after the extension of the embryo culture to the blastocyst stage), (D3T5)). Frozen blastocyst-stage embryos were transferred after warming (vitrification day 5-ET day 5 (D5T5)). Hormone replacement treatment was the only endometrial preparation regimen given during the embryo transfer cycle. The main outcome of the study was live birth rates. The clinical pregnancy rate and positive pregnancy test rate were determined as the secondary outcomes of the study. RESULTS: The study included a total of 194 patients. The positive pregnancy test rates (PPR) and clinical pregnancy rates (CPR) of the D3T3, D3T5, and D5T5 groups were 14.0% and 59.2%; 43.8% and 9.3%; and 56.3% and 39.6%, respectively (p < 0.001 and p < 0.001). The live birth rates (LBR) of patients in the D3T3, D3T5, and D5T5 groups were 7.0%, 44.7%, and 27.1%, respectively (p < 0.001). In subgroup analysis of patients with a poor number of 2PN embryos (defined as having < = 4 2PN embryos), the D3T5 group had significantly higher PPR (10.7%, 60.6%, 42.4%; p < 0.001), CPR (7.1%, 57.6%, 39.4%; p < 0.001), and LBR (3.6%, 39.4%, 21.2%; p: 0.001). CONCLUSION: Extending the culture after warming to the blastocyst stage may be a better alternative than a cleavage-stage embryo transfer.

Granulocyte colony-stimulating factor in assisted reproductive technology treatment does not increase the risk of adverse perinatal outcomes in twin pregnancies.

The aim of the study is to compare the perinatal outcomes of twin pregnancies resulting from assisted reproductive technology (ART) treatment in which granulocyte colony-stimulating factor (G-CSF) was used with those in which it was not. In this retrospective study, the clinical data of 122 dichorionic diamniotic twin pregnancies were reviewed. Pregnancies were divided into two groups, G-CSF-treated and non-G-CSF treated. Maternal age, gestational week at birth, oligohydramnios, gestational hypertension, pre-eclampsia, preterm birth, first-trimester bleeding, gestational diabetes, rupture of membrane, foetal congenital anomalies, admission to the neonatal intensive care unit, birth weight (BW), small for gestational age, BW discordance, Apgar score and placental weight were compared between the groups.IMPACT STATEMENTWhat is already known on this subject? Granulocyte colony-stimulating factor (G-CSF) administrations increase pregnancy outcomes and do not have a negative effect on perinatal outcomes in singleton pregnancies.What the results of this study add? This study showed that the perinatal outcome of dichorionic diamniotic twin pregnancies conceived after assisted reproductive technology (ART) treatment was similar in the GSF administrated and non-GSF administrated groups.What the implications are of these findings for clinical practice and/or further research? Using G-CSF to increase the success of ART does not seem to have an adverse outcome in the dichorionic diamniotic twin pregnancies.

Diet and pravastatin administration prior to in vitro fertilization treatment may improve pregnancy outcome in women with dyslipidemia.

In this study, we aimed to identify whether using statins may increase the chance of pregnancy in In Vitro Fertilisation / Intra-Cytoplasmic Sperm Injection (IVF/ICSI) patients with hyperlipidaemia. Therefore, in this retrospective cohort study, 70 patients constituted the study population and all patients were managed by lipid lowering diet. Ten mg pravastatin (pravachol DEVA, Istanbul, Turkey) was added to therapy in case of resistant hypercholesterolaemia after 15 days of the diet. Fifty-one patients were treated with diet only and the remaining nineteen patients were offered both diet and pravastatin. Clinical pregnancy rate was significantly better with the patients who used pravastatin (68.4% vs. 39.2%, p = .029). Ongoing pregnancy rates were 63.2% and 33.3% with pravastatin and diet only, respectively, which were statistically significant (p:.024). According to multivariate analysis, pravastatin use was found independently and statistically significant for clinical pregnancy and ongoing pregnancy rate after IVF/ICSI in patients with dyslipidemia (HR 3.79; 95% CI 1.31-10.97; p:.014 and HR 3.18; 95% CI 1.22-8.27; p:.018). When we analysed stratified data according to the AMH levels, we noticed that as AMH levels increased, the pregnancy rates increased; the most benefit from pravastatin was in the group with AMH levels >2 ng/mL.IMPACT STATEMENTWhat is already known on this subject? Dyslipidemia in In IVF/ICSI patients with polycystic ovary syndrome had negative impact on pregnancy ratesWhat the results of this study add? The findings of the study support that pravastatin may help to improve pregnancy outcome, especially in normal and high responders, regardless of whether decreased serum LDL or total cholesterol level.What the implications are of these findings for clinical practice and/or further research? As a result of our data, we speculated that it should be routine to investigate the lipid profile in every IVF/ICSI patient and should be treated accordingly, if necessary.

Dydrogesterone primed luteal phase stimulation may be better than follicular phase stimulation in patients with diminished ovarian reserve.

OBJECTIVE: In this study, we aimed to compare the efficacy of luteal phase stimulation (LPS) and follicular phase stimulation (FPS) in two separate menstrual cycles (2-5 months intervals) of the same patient, utilizing LPS with dydrogesteron only. METHODS: This retrospective case control study was conducted with patients with diminished ovarian reserve (DOR) (Group 1) and infertile patients with Anti-Müllerian hormone >1.2 ng/mL (Group 2) undergoing two ovarian stimulations (FPS and LPS with dydrogesteron only) and two oocyte retrievals in two separate menstrual cycles (2-5 months intervals) in the Division of Reproductive Endocrinology and Infertility of Baskent University, Ankara, between April 2019 and December 2019. RESULTS: In group 1, the number of frozen embryos was significantly higher in LPS when compared to FPS; 1.71 vs. 0.54, (p < .001), respectively. In group 2, the number of frozen embryos was higher in LPS when compared to FPS (0.8 vs. 0.4) however the difference did not reach a statistical significance (p: 0.157). CONCLUSION: LPS may be beneficial especially in the patients with diminished ovarian reserve with follicular asynchronization in the menstrual onset. In addition, it should be kept in mind that dydrogesterone only may be used instead of gonadotropin-releasing hormone antagonist to prevent possible luteinizing hormone rise in LPS.

Outcome of ICSI pregnancies with spontaneous loss of a co-twin compared with singleton ICSI pregnancies: Single center experience.

AIM: To compare the outcome of intracytoplasmic sperm injection (ICSI) pregnancies complicated by spontaneous loss of a dichorionic co-twin with that of singleton ICSI pregnancies. METHODS: The study group included dichorionic ICSI pregnancies with co-twin loss (n = 33) and the control group included ICSI pregnancies with a singleton from the beginning (n = 327). Primary outcome measures were obstetric complications, including preterm delivery, newborn small for gestational age, gestational diabetes, gestational hypertensive disorders and abruptio placenta; admission to neonatal intensive care unit (NICU) and perinatal mortality observed in the study and control groups. Statistical analysis was performed using spss for Windows, version 22.0. RESULTS: In the study group, there were 26 cases of first trimester (early) and 7 cases of second or third trimester (late) co-twin losses. Mean gestational age at delivery and mean birth weight were significantly lower in the whole study group compared to control (P < 0.05). Preterm delivery and NICU admission rates were significantly higher in the whole study group, compared to control (39.3% vs 14.6% and 36.36% vs 11.69% respectively, P < 0.05), but did not show significant difference between early loss subgroup and control (P > 0.05). Preterm delivery rate was significantly higher in the late loss subgroup compared to the early loss subgroup (85.71% vs 26.92% P < 0.05). CONCLUSION: Loss of a co-twin in dichorionic ICSI pregnancies is associated with increased risk of preterm birth. This risk is significantly higher in cases with late loss compared to the early loss cases.

Granulocyte colony-stimulating factor for intracytoplasmic sperm injection patients with repeated implantation failure: which route is best?†.

The aim of this study was to assess whether the dual administration of granulocyte colony-stimulating factor (G-CSF) increases the effect of only systemic administration in patients with RIF. This retrospective study included 111 infertile normoresponder cases with two or more unsuccessful in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatments, despite the transfer of good quality embryos. Patients were divided into three groups according to using G-CSF and administration route; Group 1 included patients who received subcutaneous (SC) G-CSF only (n = 38), Group 2 comprised patients who received both intrauterine (IU) and SC G-CSF (n = 39), the control group included patients who did not receive G-CSF who were matched by age (n = 34). The IU route of G-CSF was employed on ovulation triggering day. G-CSF was administered via an IU insemination catheter. SC injection was started on the day of oocyte retrieval and administered for 15 days at 100,000 IU/kg. Foetal cardiac activity (clinical pregnancy) was present in 50 patients (46.2%) after embryo transfer, with 20 patients included in SC group (Group 1) (52.6%), 25 in SC + IU group (Group 2) (64.1%) and 8 (23.5%) in control group and significant difference was observed between groups (p: .001). Pregnancy resulted in live birth in 43 patients (39.8%), with 13 patients belonging in Group 1 (34.2%), 25 in Group 2 (61.5%) and 8 (23.5%) in control group; significant differences were observed between groups (p: .001). In conclusion, our results showed that dual administration of G-CSF was significantly more effective that the SC only method.Impact statementWhat is already known on this subject? A number of studies reported the possible benefits of granulocyte colony-stimulating factor (G-CSF) administration in recurrent implantation failure (RIF) and recurrent pregnancy loss patients; however, it is unclear which administration route is better.What do the results of this study add? Our results showed that G-CSF is a promising and safe agent for increasing live birth rates in patients with RIF. Additionally, dual administration is considered the better method than SC only administration.What are the implications of these findings for clinical practice and/or further research? Clinicians should consider a combination of IU use before ovulation triggering with SC administration starting from the day of oocyte collection for using G-CSF for the treatment of recurrent implantation failure. Additionally, our data show the need for research in the field of administration route of G-CSF for RIF. We suggest that further studies be performed in this field.

Are There Any Predictors of Endometrial Premalignancy/Malignancy within Endometrial Polyps in Infertile Patients?

BACKGROUND: In the literature, there is no detailed analysis on the prediction factors for premalignancy/malignancy within endometrial polyps (EPs) in infertile patients. In this study, we aimed to determine the frequency of endometrial premalignancy/malignancy within EPs in infertile patients undergoing office hysteroscopic polypectomy and identify the factors that can potentially predict an endometrial premalignancy/malignancy within EPs. METHOD: A total of 957 infertile patients undergoing office hysteroscopy were diagnosed with EPs between February 2011 and August 2018. Patients were divided into 2 groups according to the pathological examination of EPs as benign (Group 1; n = 939) and premalignant/malignant (Group 2; n = 18). The medical records of all patients included in the study were reviewed retrospectively. RESULTS: In this cohort, prevalence of endometrial premalignancy/malignancy within EPs was 18/957 (1.88%). On univariate analysis, age, polyp size, diabetes, hypertension, and causes of infertility did not differ between the 2 groups. On multivariate analysis, diffuse polypoid appearance of the endometrial cavity on office hysteroscopy (hazard ratio [HR] 4.1; 95% CI 1.576-10.785), duration of infertility, (HR 4; 95% CI 1.279-12.562), and body mass index (HR 7.9; 95% CI 2.591-24.258) were found to be independent predictors of endometrial premalignancy/malignancy within polyps in infertile patients. CONCLUSION: When diffuse polypoid appearance of the endometrial cavity is detected in an infertile patient during office hysteroscopy, hysteroscopy-guided resection and endometrial curettage should be performed. The pathological specimen should be sent for histopathological evaluation to diagnose possible endometrial premalignancy/malignancy within polyps.

Effect of Etanercept on the Success of Assisted Reproductive Technology in Patients with Endometrioma.

AIMS: To determine the effects of a tumor necrosis factor inhibitor (etanercept) on pregnancy outcomes in patients with endometrioma who were treated with assisted reproductive technology. METHODS: Sixty-eight infertile patients who had endometrioma were included in our retrospective case-control study. We administered etanercept (Enbrel, 50 mg in 1 mL intramuscularly) to 19 patients on the second day of their previous menstrual cycle. All patients were treated with assisted reproductive technology. Pregnancy and live birth rates (LBR) were documented. RESULTS: When all other parameters (age, body mass index, infertility) are supposed to be constant, the clinical pregnancy rate was significantly higher in patients who used etanercept in an antagonist protocol than in patients who did not use etanercept (χ2 = 5.547; p = 0.019) but LBR did not reach a statistical significance (χ2 = 3.179; p = 0.075). The use of etanercept had an OR of 4.17 (95% CI 1.23-14.14) compared with not using etanercept for clinical pregnancy rate. The use of etanercept increased the rate of pregnancy (χ2 = 6.55; p = 0.01). The pregnancy rate with the use of etanercept had an OR of 4.23 (95% CI 1.35-13.25) compared with patients who did not use etanercept. In the same way, the use of etanercept increased LBR twofold, but it is not significant in the border line (χ2 = 3.771; p = 0.052). CONCLUSIONS: Etanercept may be a new non-hormonal therapy that may be an adjunct to treatment of infertile women with endometrioma. However, the safety of etanercept on embryos and fetuses has not been fully clarified.

Effects of amifostine on endometriosis, comparison with N-acetyl cysteine, and leuprolide as a new treatment alternative: a randomized controlled trial.

PURPOSE: To assess the effects of amifostine, N-acetyl cysteine (NAC), and leuprolide as a scavenger in a rat endometriosis model. METHODS: This is a prospective randomized animal study. Setting The Animal Laboratory of Medical University. Animals 40 rats were used for transplantation of an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. After allowing 3 weeks for growth, laparotomies were performed to check the implants. Then animals were randomized into four groups: Group I amifostine (200 mg/day loading dose after 20 mg/kg/day, p.o.); Group II NAC (200 mg/day, p.o.); Group III leuprolide acetate 1 mg/kg single dose, sc; and Group IV (controls) no medication. Three weeks later, implants were evaluated morphologically. Serum and peritoneal TNF-alpha levels were evaluated. The transmission electron microscopic examination of the peritoneal samples and ovaries was also performed. RESULTS: Leuprolide acetate, amifostine and NAC caused significant decreases in the mean implant areas and significant decreases in serum and peritoneal TNF-alpha levels. On comparing all groups, these reductions were higher in Group II. According to the transmission electron microscopic findings, leuprolide seems to be protecting normal structure of peritoneum best when compared to the other groups. CONCLUSIONS: Amifostine, NAC and leuprolide caused regression of endometriosis in this experimental rat model by a yet unsettled mechanism.

Oncologic and obstetric outcomes of early-stage epithelial ovarian cancer patients who underwent fertility-sparing surgery: A retrospective study.

OBJECTIVE: This study aimed to assess the long-term oncologic and obstetric outcomes of women with epithelial ovarian cancer who underwent fertility-sparing surgery. METHODS: A total of 68 patients observed between March 2007 and July 2021 were included in this retrospective study. Unilateral salpingo-oophorectomy and uterine preservation with staging surgery were the main procedures for fertility-sparing surgery. Disease-free, overall survival, and obstetric outcomes were measured as primary outcomes. RESULTS: The median age of the patients was 30.5 years. The median follow-up time was 60.5 months. Disease recurrence occurred in 15 (22.1%) of the patients. Five-year disease-free survival and overall survival (OS) percentages were 75.6% and 83.3%, respectively, for all stages. The FIGO (International Federation of Gynecology & Obstetrics) stage was the only significant factor that affected OS (P = 0.001). Twenty-three patients tried to conceive, and 15 (65.2%) patients became pregnant. Twelve (80%) pregnancies reached term and resulted in 15 live births. Chemotherapy administration and surgical intervention (cystectomy or unilateral salpingo-oophorectomy) showed no difference in pregnancy results (P = 0.806 and P = 0.066, respectively). CONCLUSION: Fertility preservation is safe for invasive epithelial ovarian cancer at early stages for women in the reproductive era. Disease recurrence and OS results are similar to standard treatment at early stages with decent obstetric outcomes.

Gut dysbiosis may be associated with hyperemesis gravidarum.

PURPOSE: In this study, we aimed to determine the frequency of different intestinal microorganisms of patients with normal pregnancies and HG and to compare these frequencies between the two groups. MATERIALS AND METHODS: This case-control study was carried out in Baskent University Department of Obstetrics and Gynecology and included 20 patients; 10 of whom had normal pregnancies and 10 of whom had HG. A stool flora scan was routinely planned for all patients. Transient and continuous fecal bacteria and fungal flora were analyzed. All data were evaluated statistically and their relationships with clinical condition were discussed. RESULTS: The study group consisted of 20 pregnant women with a mean age of 31.5 years. All patients were nonsmokers and free of chronic diseases and of any medications. Aerobic and anaerobic bacteria groups, fungal colonies, and parasites were examined and bowel pH values were measured separately for each patient. Bacterial and fungal species outside the reference ranges were recorded for each patient. There was a statistically significant increase in Clostridium spp. (p:.01) and Candida spp. (p:.033) and a statistically significant decrease in Bifidobacterium spp.(p:.008) in patients with HG compared to women with normal pregnancies. There was a significant difference between the group with HG and the group with normal pregnancies in terms of flora dysbiosis (p:.001). CONCLUSION: Our results suggest that gut dysbiosis may be a factor in HG. The effect of the severity of gut dysbiosis on the disease may be the subject of future studies.

Antioxidant prophylaxis for cellular injury in ovarian surface epithelium resulting from CO2 pneumoperitoneum in a laparoscopic rat model.

OBJECTIVE: Selective cytoprotective functions of vitamin E, N-acetyl-L: -cysteine, and amifostine have been used as a preventer of ischemia injury by expelling the free oxygen radicals leading to stabilization of the cellular membranes. The purpose of this experimental study was to investigate the oxidative stress related to cellular injury in ovarian surface epithelium and the effect of prophylaxis with an anti-oxidant using laparoscopic rat model. DESIGN: Laparoscopic rat model. MATERIALS AND METHODS: Randomly allocated 40 Wistar Albino female rats have been used for the pneumoperitoneum model which was constituted to fix the intraabdominal pressure on 5 mmHg for 60 min. The antioxidants, vitamin E and NAC were given to rats 3 days before the operation and were applied for 30 days; amifostine was applied 30 min before the operation until after for 7 days. After abdominal desufflation, over biopsies were made on the 13th min, 24th h, and 7th and 30th days. By using of transmission electron microscopy, the damage on cells and organels were assessed and graded. RESULTS: In ovarian surface epithelium, the apical surface specializations were affected in all groups except Vit E group:The microvilli were irregular and coarse and had disappeared in some places. Some cells were separated from the epithelium. In addition, mitochondria degeneration was observed in all group except Vit E. CONCLUSIONS: In the early period of laparoscopy, reversible cellular damage occurs and this damage can be prevented by vitamin E.

The Role of Analysis of NK Cell Subsets in Peripheral Blood and Uterine Lavage Samples in Evaluation of Patients with Recurrent Implantation Failure.

OBJECTIVE: In this study, we aimed to determine the role of analyses of NK cell subsets in peripheral blood and uterine lavage samples in evaluation of patients with unexplained RIF. METHODS: This retrospective single-institution case-control study included two different cohorts between 2017-2019. First cohort included patients examined with peripheral blood samples for evaluation of possible immunologic problems in patients with unexplained recurrent implantation failure; in the study period, a total of 75 consecutive patients with RIF (study group; n: 42) or infertile patients without RIF (control group; n: 33) were included. Second cohort included those patients whose uterine samples were assessed for immunologic problems; RIF (study group ; n: 16) or infertile patients without RIF (control group; n: 25). RESULTS: In the first cohort, the percentage of NK cells (CD3-CD16+56+) is statistically significantly lower (9.8 vs. 12.6, respectively, p: 0.038) in the study group than those of the controls whereas there was no statistical significance in the absolute number of NK cells (CD3-CD16+56+). In the second cohort, the only remarkable finding in uterine lavage samples was significantly increased uNKs cells (CD3-CD16dim56bright) percentages in controls (9.95 vs 12.7, respectively, p: 0.026) compared to those of study group. CONCLUSION: Our data shows that the analysis of NK cell subtypes in peripheral blood does not seem appropriate to investigate the patients with RIF and we suggest that uterine lavage samples instead of peripheral blood samples be implemented and evaluated.

Doxycycline causes regression of endometriotic implants: a rat model.

BACKGROUND: Doxycycline (Dox) has a number of non-antibiotic properties. One of them is the inhibition of matrix metalloproteinase (MMP) activity. The aim of this study was to assess the effects of Dox in a rat endometriosis model. METHODS: Endometriosis was surgically induced in 40 rats by transplanting of endometrial tissue. After 3 weeks, repeat laparotomies were performed to check the implants and the animals were randomized into four groups: Group I, low-dose Dox (5 mg/kg/day); Group II, high-dose Dox (40 mg/kg/day); Group III, leuprolide acetate 1 mg/kg single dose, s.c.; and Group VI (controls), no medication. The treatment, initiated on the day of surgery and continuing for 3 weeks, was administered to the study groups. Three weeks later, the rats were euthanized and the implants were evaluated morphologically and histologically for immunoreactivity of MMP-2 and -9, and interleukin-6 (IL-6) concentration in the peritoneal fluid was assayed. RESULTS: Treatment with leuprolide acetate, or high-dose or low-dose Dox caused significant decreases in the implant areas compared with the controls (P = 0.03, P = 0.006, and P = 0.001, respectively). IL-6 levels in peritoneal fluid decreased in Group I (P = 0.02) and Group III (P < 0.05). MMP H scores were significantly lower in the group that received low-dose Dox in both epithelial and stromal MMP-2 and -9 immunostaining when compared with the control group [P = 0.048, P = 0.002, P = 0.007 and P = 0.002, respectively, MMP-2 (epithelia), MMP-2 (stroma), MMP-9 (epithelia) and MMP-9 (stroma)]. CONCLUSIONS: Low-dose Dox caused regression of endometriosis in this experimental rat model.

Phosphodiesterase 4 inhibitor plus metformin is superior to metformin alone for the treatment of polycystic ovary syndrome: A rat model study.

The role of metformin in the management of polycystic ovary syndrome (PCOS) and PCOS-related obesity remains controversial. Recent research on the treatment of PCOS-related obesity investigated novel therapeutic agents with the potential to work synergistically with metformin. The aim of the present study was to determine the synergistic effect of a phosphodiesterase 4 inhibitor (PDE4i) and metformin on weight and hormonal changes in a rat model of PCOS. A total of 40 female Sprague-Dawley rats were randomly divided into 4 groups (n=10/group): Sham; PCOS control (no medication after PCOS induction with dehydroepiandrosterone); metformin (300 mg/kg/day p.o. after PCOS induction); and metformin + PDE4i (300 mg/kg/day p.o. metformin + 0.5 mg/kg/day p.o. PDE4i after PCOS induction). The body weight was measured every 7 days, from day 1 to day 49. Vaginal smears were performed and examined daily via light microscopy for determination of the stage of each rat's estrous cycle. At the end of 21st day and at the end of the study, blood samples were collected from rats and the testosterone and insulin levels were measured. Immunohistochemical staining was performed to quantify phosphorylated cyclic AMP response element-binding protein expression in all groups. At the end of the study, the median body weight differed significantly among the groups (χ2=30.581, P<0.001), being the highest in the PCOS control group and the lowest in the metformin + PDE4i group. At the end of the study, the median testosterone level differed significantly among the groups (χ2=27.057, P<0.001), being the highest in the PCOS control group and the lowest in the metformin + PDE4i group. The cycle was restored to normal at the end of the study in all the rats in the metformin and metformin + PDE4i groups, whereas an irregular cycle persisted in all the rats in the PCOS control group. In conclusion, PDE4i + metformin was superior to metformin alone in reducing weight gain and decreasing the testosterone levels in a rat model of PCOS.

Serum and follicular fluid levels of soluble Fas and soluble Fas ligand in IVF cycles.

OBJECTIVE: To determine follicular fluid (FF) and serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) in patients undergoing IVF cycles. STUDY DESIGN: A prospective comparative study among patients with endometriosis (n=12), infertility due to male factor (n=12) and poor responders (n=32) undergoing IVF cycles in Centrum IVF Clinic. Individual FF and serum samples were collected from patients during transvaginal ultrasonography-guided follicle aspiration. Patients were classified as poor responder patients undergoing IVF cycles with GnRHa, triptorelin and GnRH antagonist, cetrotide, patients with endometriosis and patients with infertility due to male factor. sFas, sFasL levels in both FF and serum samples and their correlations with clinical outcomes of IVF were measured in each study group. RESULTS: Serum and FF levels of sFas, sFasL were similar in the poor responder and male factor groups. There were no differences between the serum and FF levels of both sFas and sFasL among poor responder patients receiving either GnRH agonist or antagonist therapies. Serum levels of sFas were significantly lower in the endometriosis group compared to the male factor group. Serum and FF levels of sFas, sFasL were similar among patients with or without clinical pregnancy. CONCLUSION: sFas and sFasL are detected in both serum and follicular fluid samples from IVF cycles, their levels are similar between poor responder and male factor groups as well as between GnRH agonist and antagonist treatment groups. These soluble apoptotic factors may not be predictive for the outcomes of IVF. Decreased serum levels of sFas, suggests increased apoptosis in endometriosis.

Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: obese, lean, hyper or normoinsulinemic?

OBJECTIVE: The aim of the present study is to evaluate sub-groups of PCOS patients who will benefit from metformin therapy and to find out any predictors of ovulation in PCOS sub-groups. METHOD: In the current prospective-randomized, placebo-controlled, double-blind study, PCOS patients (n = 116) were divided into six main groups according to glucose to insulin ratio (G-I ratio mg/10(-4) U) and body mass index (BMI kg/m2) as: Group 1: normoinsulinemic (G-I ratio > or = 4.5 mg/10(-4) U), lean (BMI < 25) (n = 37); Group 2: normoinsulinemic, overweight (BMI: 25-29.9) (n = 19); Group 3: normoinsulinemic, obese (BMI > or = 30) (n = 18); Group 4: hyperinsulinemic (G-I ratio < 4.5 mg/10(-4) U), lean (n = 28); Group 5: hyperinsulinemic, overweight (n = 17); Group 6: hyperinsulinemic, obese (n = 20). Patients in each group were randomized onto placebo or metformin treatments (850 mg two to three times per day according to BMI). The rate of ovulation, biochemical profile, hormonal profile and clinical symptoms of hyperandrogenism were evaluated before and after 6 months of metformin and placebo treatments. RESULT(S): We observed a significant decrease in WHR following metformin therapy in the normoinsulinemic overweight sub-group (P < 0.05). The duration of the menstrual cycle significantly decreased in the normoinsulinemic obese sub-group on metformin therapy (P < 0.05). Metformin had a significant effect on hirsutism scores in hyperinsulinemic lean women (P < 0.05) and decreased DHEAS levels significantly in the lean hyperinsulinemic and normoinsulinemic groups (P < 0.05). Metformin had significant effects on ovulation in only lean hyperinsulinemic women (P < 0.05). CONCLUSIONS: Clinical outcomes of metformin therapy may be categorized on the basis of basal BMI and insulin levels in PCOS patients.

Aspiration of ovarian endometriomas before intracytoplasmic sperm injection.

OBJECTIVE: To investigate whether aspiration of ovarian endometriomas before controlled ovarian stimulation (COH) improves intracytoplasmic sperm injection (ICSI) outcomes. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): A prospective analysis of 171 patients with ovarian endometriosis and tubal factor infertility were divided into four groups: aspiration of endometriomas at the beginning of COH in patients with ovarian endometriomas and no history of previous surgery (n = 41) (group 1); nonaspirated endometriomas (n = 40) (group 2); history of ovarian surgery for endometriomas in patients without ovarian endometriomas at the beginning of COH (n = 44) (group 3); and tubal factor infertility (n = 46) (control group 4). INTERVENTION(S): Aspiration of endometriomas. MAIN OUTCOME MEASURE(S): Clinical parameters, characteristics of COH, and ICSI results were analyzed. RESULT(S): We observed higher levels of E(2) on the day of hCG injection after aspiration of endometriomas compared with nonaspirated endometriomas. When we compared all endometriomas and tubal factor (control) groups, we observed a lower number of total follicles (>17 mm) and metaphase II (MII) oocytes in nonaspirated and resected endometrioma groups and a longer duration of COH in the nonaspirated endometrioma group compared with the tubal factor group. Implantation and clinical pregnancy rates were similar among all groups. CONCLUSION(S): In the current study, all patients with endometriomas had significantly lower numbers of MII oocytes compared with those in patients with tubal factor infertility. We propose that aspiration of endometriomas before COH neither reduces the amount of gonadotropins nor increases the number of follicles >17 mm, the number of MII oocytes retrieved, the implantation rates, or the clinical pregnancy rates. Resection of small endometriomas (1-6 cm) may not present any additional benefits to the IVF-ICSI cycle outcomes.

Remedies for recurrent implantation failure.

In vitro fertilization (IVF) is expensive, time consuming, and the most successful treatment of fertility; however, in general the cumulative chance of having a live birth with the treatment is still around 40%. Many couples still remain unsuccessful after several IVF attempts, causing deep impact on quality of life, and each failed cycle causing a financial burden. Several adjuvant therapies have been used along with IVF to increase the pregnancy rates for women with repeated implantation failure. Testing of adjuvant therapies in properly conducted randomized controlled trials is rarely done so that potential benefits and risks are unlikely to be clearly presented to patients and clinicians. In this review, we assessed the effects of adjuvants, such as growth hormone, androgens, and glucocorticoids to enhance oocyte number and quality; sildenafil, low-dose aspirin, heparin, corticosteroids, granulocyte colony-stimulating factor, endometrial injury, intrauterine injection of human chorionic gonadotropin, and intrauterine administration of autologous peripheral blood mononuclear cells to improve poor endometrial response; antioxidants, complementary and alternative medicine modalities, such as Chinese herbal medicine and acupuncture; and assisted hatching and preimplantation genetic screening to correct embryonic factors.