Gogsen Onalan

Body mass index is an independent risk factor for the development of endometrial polyps in patients undergoing in vitro fertilization

OBJECTIVE To determine the subgroup of patients in whom office hysteroscopy should be routinely performed before an in vitro fertilization (IVF) program. DESIGN Retrospective cohort analysis. SETTING Tertiary education and research hospital. PATIENT(S) Two hundred twenty-three patients who underwent a uterine evaluation by office hysteroscopy before the IVF and embryo transfer cycle. INTERVENTION(S) The office hysteroscopy was performed in the follicular phase of the menstrual cycle before the IVF cycle. MAIN OUTCOME MEASURE(S) The office findings: number of polyps, number of multiple polyps, and polyp size. RESULT(S) Patients with polycystic ovary syndrome (PCOS) had a higher number of endometrial polyps, but the difference was not statistically significant (28.9% vs. 18.3%). When comparing the patients according to BMI, patients with BMI >or=30 had a statistically significantly higher number of endometrial polyps versus BMI <30 (52% vs. 15%). On the other hand, obesity was positively correlated with the occurrence of polyps, size of the polyps, and occurrence of multiple number of polyps in the correlation analysis. In addition, logistic regression analysis using age, obesity, duration of infertility, and estradiol levels revealed that obesity was an independent prognostic factor for the development of endometrial polyps. CONCLUSION(S) Office hysteroscopy should be performed in patients with BMI >or=30 because obesity may act as an initiator for the pathogenesis of endometrial polyps.

Efficiency and pregnancy outcome of serial intrauterine device-guided hysteroscopic adhesiolysis of intrauterine synechiae.

OBJECTIVE To highlight the efficiency of intrauterine device (IUD) guidance during hysteroscopic adhesiolysis for severe intrauterine adhesions. DESIGN A prospective, randomized trial. SETTING Private tertiary and referral infertility clinic. PATIENT(S) Seventy-one subfertile patients who underwent hysteroscopic treatment of intrauterine synechiae or adhesions. INTERVENTION(S) Thirty-six women in group 1 were initially examined by laparoscopy-hysteroscopy at first look, and an IUD was inserted during hysteroscopic adhesiolysis. The adhesions were further lysed by the guidance of IUD during the second-look office hysteroscopy, 1 week later. Patients were prescribed 2 months of estrogen as well as P therapy, and the IUD was removed by the end of this period. The uterine cavity was evaluated, and adhesions were further lysed by a third-look office hysteroscopy, 1 week after the removal of IUD. Thirty-five women in group 2 were similarly examined by first-look office hysteroscopy, and an IUD was inserted during hysteroscopic adhesiolysis. These patients did not undergo early intervention of office hysteroscopy, 1 week after the first procedure. They also used 2 months of estrogen and P therapy. The IUD was removed by the end of this period, and the uterine cavity was evaluated and adhesions were further lysed during a second-look office hysteroscopy. MAIN OUTCOME MEASURE(S) Pregnancy rate and live birth rate. RESULT(S) Spontaneous pregnancy rates after treatment were 17/36 (47.2%) and 11/35 (30%), and live birth rates were 10/36 (28%) and 7/35 (20%) in groups 1 and 2, respectively. These differences between the two groups were not statistically significant. CONCLUSION(S) The method described especially for early intervention may prevent complications during the treatment of severe intrauterine adhesions and may present a secure and effective alternative for constructive clinical outcomes.

Inherited mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) in empty follicle syndrome

OBJECTIVE To test by genomic analysis whether empty follicle syndrome (EFS) in a family with two affected sisters has a genetic basis. DESIGN Whole-exome sequencing in the context of clinical genetics. SETTING University hospital. PATIENT(S) Two women (36 and 32 years old at the time of the study) with EFS. INTERVENTION(S) Genetic counseling based on autosomal recessive inheritance. MAIN OUTCOME MEASURE(S) Discovery of a mutation in the LH/choriogonadotropin receptor (LHCGR) as the cause of EFS. RESULT(S) A novel missense mutation in LHCGR, p.N400S, was homozygous in sisters with EFS and/or infertility, but not in their unaffected siblings or parents. The mutation was not present in 500 ancestry-matched control subjects. Asparagine at residue 400 is highly conserved and its substitution by serine predicted to alter critical interactions that stabilize LHCGR. CONCLUSION(S) We describe a genetic basis for EFS and provide strong evidence for the existence of genuine EFS in some patients. A mutation impairing the function of LHCGR explains the lack of response of these patients to repeated administration of β-hCG.

Combining 2nd-trimester maternal serum homocysteine levels and uterine artery Doppler for prediction of preeclampsia and isolated intrauterine growth restriction.

Aim: To evaluate the efficacy of a combined 2nd-trimester maternal serum homocysteine and uterine artery Doppler screening at 20 weeks of gestation for complications of pregnancy: preeclampsia, isolated intrauterine growth restriction (IUGR), placental abruption, and stillbirths. Methods: Consecutive singleton pregnancies without previous risk factors who had homocysteine measured as part of a serum-screening program for trisomy 21 had uterine artery Doppler performed. Sensitivity, specificity, positive and negative predictive values, odds ratio, and positive and negative likelihood ratios for the subsequent development of preeclampsia, isolated IUGR, placental abruption, stillbirth, and preterm delivery were calculated for the following methods (1) homocysteine cutoff level 6.3 µmol/l (95th centile); (2) on Doppler ultrasound bilateral notches with a mean resistance index (RI) >0.55 (50th centile), all unilateral notches with a mean RI >0.65 (80th centile), and absence of notches with a mean RI >0.7 (95th centile), and (3) Doppler ultrasound notch evaluation (bilateral, unilateral, absence as in method 2) combined with the homocysteine cutof level of 6.3 µmol/l. Results: By using a logistic regression model, methods 1 and 2 predicted preeclampsia (p < 0.001), isolated IUGR (p < 0.01), and ‘any complication’ (p < 0.01). The sensitivity for prediction of preeclampsia using the combined method (3) was 61.3% for a false-positive rate of 2%, better than that for isolated IUGR (54%) below the 5th centile and ‘any complication’(56%). Conclusion: This prospective study confirms the potential of a combined method of elevated homocysteine and uterine artery Doppler screening for preeclampsia, isolated IUGR, and any obstetric complication.

Sublingual misoprostol for cervical ripening before diagnostic hysteroscopy in premenopausal women: a randomized, double blind, placebo-controlled trial.

OBJECTIVE To evaluate the effectiveness of sublingual misoprostol for cervical ripening before diagnostic hysteroscopy in premenopausal women. DESIGN Placebo-controlled, double-blind, randomized trial. SETTING University hospital. PATIENT(S) Fifty-two women with an indication for diagnostic hysteroscopy. INTERVENTION(S) Randomized women who had received either 200 mug of misoprostol (n = 25) or placebo (n = 27) sublingually 2 hours before hysteroscopy. Two subgroups (women with or without previous vaginal delivery) were formed. MAIN OUTCOME MEASURE(S) Number of women requiring cervical dilatation, duration of dilatation, ease of dilatation, and complications during procedure. RESULT(S) In the misoprostol group, 14 patients needed cervical dilatation, versus 21 in the placebo group. Duration of dilatation was longer in the placebo group than in the misoprostol group. In subgroup 1, seven patients in the misoprostol group (n = 13) and nine patients in the placebo group (n = 12) needed cervical dilatation. The duration of the dilatation was similar between the groups. In subgroup 2, both the need for cervical dilatation (58.3% vs. 80.0%) and the duration of dilatation (31.0 +/- 18.8 vs. 73.0 +/- 82.0 seconds) were found to be lower in the misoprostol (n = 15) than in the placebo (n = 12) group, respectively. Those differences were all not significant. CONCLUSION(S) Sublingual misoprostol before diagnostic hysteroscopy did not seem to facilitate cervical ripening statistically; however, the results are remarkable and are promising clinically. Further studies are required to reassess the use of sublingual misoprostol in patients before hysteroscopy.

Comparison of the effectiveness of single versus double intrauterine insemination with three different timing regimens

OBJECTIVE To compare double insemination with two different single insemination regimens. DESIGN Prospective study. SETTING Tertiary education and research hospital. PATIENT(S) Four hundred and fifty patients with unexplained infertility, male factor, and ovulatory dysfunction underwent controlled ovarian hyperstimulation with gonadotropin. INTERVENTION(S) The patients were divided randomly into three groups: patients in group 1 underwent a single preovulatory intrauterine insemination (IUI) performed 24 hours after hCG administration. Patients in group 2 underwent two IUIs performed 12 and 36 hours after hCG administration. Patients in group 3 underwent a single periovulatory IUI performed 36 hours after hCG administration. MAIN OUTCOME MEASURE(S) Pregnancy rate. RESULT(S) The total pregnancy rate per patient was 14.2 % (64 pregnancies in 450 patients). Group 1 had 17 pregnancies (11.3%), while groups 2 and 3 had 21 (14.0%) and 26 (17.2%) pregnancies, respectively. The difference between the three groups in regard to pregnancy rates was statistically not significant. CONCLUSION(S) Despite the 36th hour being the preferred timing for IUI, there was no difference regarding pregnancy rates between single 24th hour and double 12th- and 36th-hour inseminations. This finding suggests that the 24th-hour IUI might be preferred in demanding situations.

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.

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.

Fenofibrate causes regression of endometriotic implants: a rat model

Fenofibrate -a peroxisome proliferator-activated receptor-a agonist- is an angiostatic agent that is commonly used in human liver diseases, therefore it may interfere with the angiogenetic process required for endometriosis. In a rat endometriosis model, we demonstrated that peritoneal implant areas and vascular endothelial growth factor levels in the peritoneal flud were significantly decreased in high dose or low dose finofibrate and luprolide acetate treated groups compared to control.

Successful pregnancy with preimplantation genetic diagnosis in a woman with mosaic Turner syndrome.

OBJECTIVE To determine the efficacy of the preimplantation cytogenetic analysis of the embryos obtained from patient with mosaic Turner syndrome before an IVF program. DESIGN Prospective cytogenetic analysis. SETTING University-based tertiary medical center. PATIENT(S) A 29 year-old female, a partner in a couple with male factor infertility, was diagnosed with mosaic Turner syndrome with a 45,X [17]/46,XX [13] karyotype. INTERVENTION(S) Preimplantation genetic diagnosis was performed on four blastomeres obtained from four different embryos by fluorescence in situ hybridization probes specific to chromosomes X, Y, 13, 18, 21 in an intracytoplasmic sperm injection cycle. MAIN OUTCOME MEASURE(S) Blastomeres with normal signals. RESULT(S) Two blastomeres detected as normal were transferred and pregnancy was achieved. CONCLUSION(S) Preimplantation Genetic Diagnose should be considered in the infertility treatment of the patient with mosaic Turner Syndrome.