The effect of swim-up and gradient sperm preparation techniques on deoxyribonucleic acid (DNA) fragmentation in subfertile patients.

PURPOSE: To compare the effect of two different sperm preparation techniques, including swim-up and gradient methods on sperm deoxyribonucleic acid (DNA) fragmentation status of semen samples from unexplained and mild male factor subfertile patients undergoing intrauterine insemination (IUI). DESIGN: A prospective randomized study was conducted in 65 subfertile patients, including 34 unexplained and 31 male factor infertility to compare basal and post-procedure DNA fragmentation rates in swim-up and gradient techniques. Sperm DNA fragmentation rates were evaluated by a sperm chromatin dispersion (SCD) test in two portions of each sample of semen that was prepared with either swim-up or gradient techniques. Sperm motility and morphology were also assessed based on WHO 2010 criteria. RESULTS: Swim-up but not gradient method yielded a statistically significant reduction in the DNA fragmented sperm rate after preparation as compared to basal rates, in the semen samples of both unexplained (41.85 ± 22.04 vs. 28.58 ± 21.93, p < 0.001 for swim-up; and 41.85 ± 22.04 vs. 38.79 ± 22.30, p = 0.160 for gradient) and mild male factor (46.61 ± 19.38 vs. 30.32 ± 18.20, p < 0.001 for swim-up and 46.61 ± 19.38 vs. 44.03 ± 20.87, p = 0.470 for gradient) subgroups. CONCLUSIONS: Swim-up method significantly reduces sperm DNA fragmentation rates and may have some prognostic value on intrauterine insemination in patients with decreased sperm DNA integrity.

Elevated basal progesterone levels are associated with increased preovulatory progesterone rise but not with higher pregnancy rates in ICSI cycles with GnRH antagonists.

OBJECTIVE: To ascertain the association between basal progesterone (P) levels and the occurrence of preovulatory progesterone rise (PPR) and clinical pregnancy rates (CPRs) in ICSI cycles with GnRH antagonists. STUDY DESIGN: Serum P levels of 464 patients were measured on day 2 and day of hCG of cycles. Cycles with basal P levels>1.6ng/mL were cancelled. All embryos were cryopreserved in cycles with P levels≥2ng/mL on the day of hCG. The primary outcome measures were the incidence of PPR (P>1.5ng/mL) and CPR with regard to basal P. RESULTS: Basal P levels were significantly higher in cycles with PPR than in those without PPR (0.63±0.31 vs. 0.48±0.28ng/mL). Area under the curve for basal P according to ROC analysis to discriminate between elevated and normal P levels on the day of hCG was 0.65 (0.58-0.71 95% CI, p<0.01). The cut-off value for basal P levels that best discriminates between cycles with and without PPR was 0.65ng/mL. Cycles with basal P levels above 0.65ng/mL had a significantly higher incidence of PPR (30.9% vs. 13.5%) but similar clinical and cumulative pregnancy rates (38.8% vs. 31.1% and 41.7% vs. 32.6%, respectively) in comparison to cycles with basal P levels below 0.65ng/mL. In multivariate regression analysis, basal P levels, LH level on the first day of antagonist administration, and estradiol levels on the day of hCG trigger were the variables that predicted PPR. CONCLUSION: Basal P levels were associated with increased incidence of PPR but not with CPR.

The Impact of laparoscopic surgery of peritoneal endometriosis and endometrioma on the outcome of ICSI cycles.

Our objective was to assess the role of laparoscopic removal of ovarian endometriomas and ablation of peritoneal endometriosis on the outcome of intracytoplasmic sperm injection (ICSI) - Embryo Transfer cycles by comparing with the results of patients with untreated endometriomas and tubal factor without underlying endometriosis confirmed by laparoscopy. For this purpose, between 2002 and 2015, outcomes of 257 ICSI cycles of 150 patients, including 91 cycles of 48 patients in minimal endometriosis, 57 cycles of 25 patients in endometrioma removal, 65 cycles of 53 patients in non-operated endometrioma, and 44 cycles of 24 patients in tubal factor groups were retrospectively analyzed. Basal ovarian reserve was significantly lower, mean starting and total gonadotropin consumption was significantly higher, and mean serum E2 on the day of hCG injection, number of dominant follicles, number of retrieved total, and MII oocytes were all significantly lower in the endometrioma cystectomy group. Fertilization and embryo cleavage rates were also significantly the lowest in the endometrioma cystectomy group, whereas clinical pregnancy and live birth rates were comparable among all groups. The number of transferred embryos and duration of infertility were the most significant predictors of clinical pregnancy and live birth. Basal antral follicle count was also significant in predicting live birth.

Comparison of the standard GnRH antagonist protocol and the luteal phase estradiol/GnRH antagonist priming protocol in poor ovarian responders.

BACKGROUND/AIM: The aim of the study was to compare the luteal estradiol patch/GnRH antagonists priming protocol (LPP) with the standard GnRH antagonist protocol in poor ovarian responders (PORs) in terms of the outcomes of in vitro fertilization (IVF) treatment. MATERIALS AND METHODS: IVF outcomes of 265 cycles in 265 patients (106 in the LPP group, 159 in the standard GnRH antagonist group) were evaluated retrospectively. RESULTS: Mean length of stimulation (11.4 ± 2.7 vs. 10.0 ± 2.7 days; P < 0.05) and the total gonadotropin dose (3403 ± 1060 vs. 2984 ± 1112) used were significantly greater in the LPP group than in the standard GnRH antagonist protocol group. The mean number of oocytes retrieved (3.5 ± 2.6 vs. 3.7 ± 2.8), the number of mature oocytes (2.8 ± 2.2 vs. 2.6 ± 2.2), fertilization rates (65% vs. 62%), the number of embryos transferred (1.6 ± 0.6 vs. 1.7 ± 0.6), and implantation rates (16% vs. 13%) were similar. The cancellation rate did not significantly differ between the groups (9.4% vs. 13.2%). There were no significant differences in the clinical pregnancy (11.3% vs. 13.2%) or live birth rates per patient (3.8% vs. 9.4%) and clinical pregnancy (18.8% vs. 22.6%) or live birth rates per embryo transfer (6.3% vs. 12.9%) between the groups. CONCLUSION: LPP does not improve IVF outcomes when compared with the standard GnRH antagonist protocol in PORs.

Two cases of first onset intrahepatic cholestasis of pregnancy associated with moderate ovarian hyperstimulation syndrome after IVF treatment and review of the literature.

Intrahepatic cholestasis of pregnancy (ICP) is an uncommon disorder, which generally occurs in the second and third trimester of pregnancy with symptoms of pruritus. The cause of ICP is unknown but genetic, hormonal and environmental factors contribute to its pathogenesis. The aetiology of ICP is unclear but elevation in oestrogen levels thought to cause ICP is typically seen in the third trimester of pregnancy, and for this reason it is not usually considered in the differential diagnosis of pruritus and liver function disorders in the first trimester of the pregnancy. We present two cases of pregnancy after IVF treatment diagnosed with ICP following the development of OHSS, deteriorating liver function tests and severe pruritus.

Comparison of age-related changes in anti-Müllerian hormone levels and other ovarian reserve tests between healthy fertile and infertile population.

In this study, we aimed to determine whether anti-Müllerian hormone (AMH) levels vary between fertile and infertile populations and compare them with basal follicle-stimulating hormone (FSH) levels and antral follicle count (AFC). This was a prospective study that included 177 primarily infertile patients who underwent IVF treatment and 162 healthy fertile patients admitted to our clinic for benign diseases. FSH and AMH levels and the AFC of the infertile and fertile populations were compared between the age categories <30, 30-39 and ≥40. Correlations between AMH, basal FSH, and AFC with age were evaluated. AFC and AMH levels did not differ between the fertile and infertile groups in all age categories. AMH was inversely correlated with age in both the fertile and infertile populations. However, AFC revealed a stronger correlation with age in both the fertile and infertile populations compared with basal FSH and AMH. Age was positively correlated with basal FSH and inversely correlated with AMH and AFC. In conclusion, there was no significant difference between the fertile and infertile populations in terms of AMH or AFC. The decrease in ovarian reserve in infertile patients is directly related to age, not infertility.

The impact of premature progesterone rise on the outcome of intrauterine insemination cycles with controlled ovarian hyperstimulation in unexplained infertility.

OBJECTIVE: To ascertain the incidence of premature progesterone P rise and its impact on outcomes in controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI) cycles, and also to identify variables related with premature P rise. STUDY DESIGN: Four hundred sixty cycles of 460 couples with unexplained infertility having COH-IUI treatment with a starting dose of 75IU recombinant FSH enrolled in this prospective study. Serum P levels were determined on the day of hCG trigger. Premature P rise was defined as progesterone ≥1ng/mL. The primary outcome measure was live birth per cycle with regard to P levels of ≥1ng/mL and ≥1.5ng/mL. Secondary outcome measures were cycle characteristics associated with P rise. RESULTS: The incidence of premature P rise was 22.0%. P levels on hCG day were significantly lower in cycles with live birth as compared to cycles without live birth 0.49±0.51 vs. 0.73±0.82ng/mL. Live birth rates were significantly lower in cycles with hCG day P levels ≥1.0ng/mL (%7.9 vs. %22.6) and ≥1.5ng/mL (%6.4 vs. %20.8). Among age, number of dominant follicles, estradiol, LH and P levels on the day of hCG trigger, it was found that P levels was the only significant variable to predict live birth on multivariate analysis. The number of dominant follicles on hCG day and premature LH surge were the only significant variables related with premature P rise. CONCLUSION: Premature P is a frequent feature of COH-IUI cycles and associated with decreased live birth rates.

The impact of sperm morphology on the outcome of intrauterine insemination cycles with gonadotropins in unexplained and male subfertility.

OBJECTIVE: To determine the impact of sperm morphology on success of intrauterine insemination (IUI) in unexplained and male subfertility. STUDY DESIGN: Basal and post-wash normal percentage of sperm with normal morphology was assessed prospectively in 412 couples with 530 IUI cycles who underwent ovarian hyperstimulation with gonadotropins. The primary outcome was live birth per cycle. Receiver operating characteristics (ROC) curves were used to determine the effectiveness of sperm morphology to predict live birth in IUI cycles. RESULTS: Normal sperm morphology (%) after preparation was higher in patients with live birth (5.4 ± 4.5 vs 4.3 ± 4.1; respectively, p<.05) in study population. In male subfertile group, normal sperm morphology before and after sperm preparation was higher in patients with live birth (1.3 ± 1.4 vs 0.6 ± 0.9; p<0.001 and 4.6 ± 4.4 vs 1.9 ± 2.2; p<0.01, respectively). However, both basal and post-wash normal sperm morphology (%) were similar in patients with and without live birth in unexplained group. The best cut-off value for normal sperm morphology (%) to predict live birth was 4.5% in male subfertile group with a sensitivity of 50.6% and specificity of 61.7%. CONCLUSION: Morphological evaluation is not a reliable parameter alone for predicting pregnancy outcome in unexplained infertility. In male subfertility, post-wash normal sperm morphology percentage higher than 4.5 increases the probability of live birth.

Effects of anticoagulant therapy on pregnancy outcomes in patients with thrombophilia and previous poor obstetric history.

This study investigates the effects of anticoagulant therapy on pregnancy outcomes in 204 patients with thrombophilia and previous poor obstetric outcomes. Patients with poor obstetric history (pre-eclampsia, intrauterine growth retardation, fetal death, placental abruption, recurrent pregnancy loss) and having hereditary thrombophilia were included in this study. Poor obstetric outcomes were observed more frequently in patients who had not taken anticogulant therapy compared with treated group. Live birth rate, gestational age at birth and Apgar scores were significantly higher in the treated group when compared with the untreated group. There were no significant differences in terms of birthweight, mode of delivery and admission rates to the neonatal intensive care unit (NICU). Low-molecular-weight heparin (LMWH) plus acetylsalicylic acid (ASA) had higher gestational age at birth, Apgar scores, live birth rate and a lower abortion rates when compared with controls; in contrast, no significant difference was observed in terms of birthweight, mode of delivery, obstetric complications and admission rates to NICU. There were no significant differences between control group and both LMWH only and ASA only groups in terms of gestational age at birth, Apgar scores, birthweight, mode of delivery, obstetric complications and admission rates to NICU. Only LMWH group had higher live birth rate as compared with control group. The use of only ASA did not seem to affect the perinatal complication rates and outcomes. In conclusion, anticoagulant therapy with both LMWH and ASA seems to provide better obstetric outcomes in pregnant women with thrombophilia and previous poor obstetric outcomes.

Comparison of ovulation induction protocols after endometrioma resection.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the in vitro fertilization (IVF) outcomes of long gonadotropin-releasing hormone agonist (GnRH-a) and GnRH-antagonist (GnRH-ant) protocols in endometriosis patients who have undergone laparoscopic endometrioma resection surgery. To our knowledge, there is no study in the current literature that compares the effectiveness of long GnRH-a and GnRH-ant protocols in management of IVF cycles in endometriosis patients who underwent laparoscopic endometrioma resection surgery. METHODS: Eighty-six patients with stage III to IV endometriosis who had undergone laparoscopic resection surgery for endometrioma were divided into 2 groups: those who had ovarian stimulation with a long GnRH-a protocol (n=44), and those who had ovarian stimulation with a GnRH-ant protocol (n=42). RESULTS: The number of follicles on human chorionic gonadotropin injection day, duration of hyperstimulation, number of retrieved metaphase II oocytes, and total number of grade 1 embryos were statically significantly higher in the long GnRH-a protocol. There were no significant differences in positive ß-human chorionic gonadotropin pregnancy rates (25% vs 21.4%; P=.269) and ongoing pregnancy rates per patient (20.5% vs 19.1%; P=.302) between the 2 protocols. CONCLUSIONS: Long GnRH-a and GnRH-ant protocols both present similar IVF outcomes in patients with endometriosis who have undergone laparoscopic endometrioma resection surgery. A long GnRH-a protocol may lead to a higher number of embryos that can be cryopreserved, providing the possibility of additional embryo transfers without having to go through the process of ovarian stimulation again.

The gradient technique improves success rates in intrauterine insemination cycles of unexplained subfertile couples when compared to swim up technique; a prospective randomized study.

PURPOSE: To compare the efficacy of gradient and swim-up semen preparation techniques on pregnancy rates in couples undergoing intrauterine insemination (IUI) cycles with low dose gonadotropin stimulation with the diagnosis of unexplained or mild male subfertility. METHODS: Two hundred and twenty three couples were randomized into swim up or gradient technique groups for sperm preperation. The clinical and on going pregnancy rates per cycle and per patient were evaluated. RESULTS: Both clinical and ongoing pregnancy rates per cycle were significantly higher in the "gradient" group (19% and 16.9%) in comparision with the "swim up" group (9.7% and 6.9%) (p < 0.05). Clinical pregnancy and on-going pregnancy rates per patient were higher in the "gradient" group (26.1% and 23.4%) when compared to the "swim up" group (15.2% and 10.7%), (p < 0.05). In the subgroup of 191 unexplained subfertile couples with 290 cycles; the "gradient" group also revealed significantly higher clinical and ongoing pregnancy rates per cycle (21.6% and 17.9%) when compared with the "swim up" group (10.3% and 7.1%) (p < 0.05). In total of 48 treatment cycles upon 32 couples with mild male factor subfertility no significant difference were found between the two sperm preparation techniques in terms of clinical (% 5.3 vs %6.9, p > 0.05) and ongoing (% 5.3 vs %6.9, p > 0.05) pregnancy rates per cycle. CONCLUSION: The gradient technique significantly improves clinical outcome in IUI cycles of unexplained subfertile couples when compared to swim up technique. In male subfertile patients, both techniques yield similar clinical outcomes.

Can uterine artery Doppler parameters predict copper intrauterine device-induced side effects?

OBJECTIVES To evaluate the predictive value of uterine artery Doppler characteristics in predicting copper intrauterine device (IUD)-induced side effects such as dysmenorrhoea and menorrhagia, and worsening of dyspareunia. METHODS One hundred and twenty regularly menstruating women were enrolled in the study. All underwent transvaginal uterine artery Doppler analysis in the early follicular phase, on two occasions: before insertion of the IUD, and six months after insertion. Pre- and post-insertion resistance (RI) and pulsatility (PI) indices of the uterine arteries were measured. Doppler parameters were compared between subjects experiencing an increase in IUD-mediated side effects and those reporting no change. RESULTs RI and PI of all participants before and after IUD insertion were not significantly different (0.75 ± 0.06 vs. 0.74 ± 0.09, p = 0.49; 1.81 ± 0.55 vs. 1.83 ± 0.70, p = 0.7, respectively). No significant difference was found in the comparison of pre- and post-insertion PI and RI values of women who had increased- and those who experienced no change in dysmenorrhoea, dyspareunia and duration/amount of menstruation. CONCLUSIONS No major changes in uterine blood flow were observed in women experiencing increased menstrual bleeding, dyspareunia or dysmenorrhoea after insertion of a copper IUD. The occurrence of these effects cannot be predicted by prior Doppler flow analysis.

Antral follicle count determines poor ovarian response better than anti-Müllerian hormone but age is the only predictor for live birth in in vitro fertilization cycles.

PURPOSE: To determine the predictive value of serum anti-müllerian hormone (AMH) concentrations and antral follicle counts (AFC), on ovarian response and live birth rates after IVF and compare with age and basal FSH. METHODS: Basal levels of AMH, FSH and antral follicle count were measured in 192 patients prior to IVF treatment. The predictive value of these parameters were evaluated in terms of retrieved oocyte number and live birth rates. RESULTS: Poor responders in IVF were older, had lower AFC and AMH but higher basal FSH levels. In multivariate analysis AFC was the best and only independent parameter among other parameters and AMH was better than age and basal FSH to predict poor response to ovarian stimulation. Addition of AMH, basal FSH, age and total gonadotropin dose to AFC did not improve its prognostic reliability. Area under curve (AUC) for each parameter according to ROC analysis also revealed that AFC performed better in poor response prediction compared with AMH, basal FSH and age. The cut-off point for mean AMH and AFC in discriminating the best between poor and normal ovarian response cycles was 0.94 ng/mL (with a sensitivity of 70% and a specificity of 86%) and 5.5 (with a sensitivity of 91% and a specificity of 91%), respectively. However, age was the only independent predictor of live birth in IVF as compared to hormonal and ultrasound indices of ovarian reserve. CONCLUSION: AFC is better than AMH to predict poor ovarian response. Although AMH and AFC could be used to predict ovarian response they had limited value in live birth prediction. The only significant predictor of the probability of achieving a live birth was age.

Treatment of vaginal agenesis using a modified McIndoe technique: Long-term follow-up of 23 patients and a literature review.

BACKGROUND: Congenital vaginal agenesis is a rare malformation with an incidence of one in 4000 to 5000 female newborns. The purpose of vaginal agenesis treatment is not only to create an adequate passageway for penetration but also to facilitate satisfactory sexual intercourse. OBJECTIVE: To present the results of a modified McIndoe technique with respect to sexual function, vaginal length and complication rates in patients with vaginal agenesis. METHODS: Between 2002 and 2010, 23 patients with vaginal agenesis were admitted to the Gynecology Clinic of Istanbul University School of Medicine (Istanbul, Turkey) for vaginal reconstruction. All patients underwent a modified McIndoe procedure. The long-term results with a follow-up period ranging from 18 to 118 months are presented. RESULTS: The postoperative mean vaginal length was 8.4 cm (range 6 cm to 11 cm) in 19 patients who used the mould regularly. Among 14 patients who used the mould regularly and had partners, only one experienced severe pain during intercourse and 13 reported that they were engaging in satisfactory sexual activity with mild or no pain, and with good mucosal sensitivity. Conversely, two of three patients who used the mould irregularly experienced severe pain during intercourse and had a mean vaginal length of 6 cm (range 4 cm to 8 cm). CONCLUSION: The findings suggest that a modified McIndoe technique is a simple, effective procedure for the treatment of vaginal agenesis; however, proper mould use after surgery remains the cornerstone of the treatment.

HISTORIQUE: L'agénésie vaginale congénitale est une malformation rare à l'incidence de un cas sur 4 000 à 5 000 nouveau-nés de sexe féminin. Le traitement de l'agénésie vaginale vise non seulement à créer un passage suffisant pour la pénétration, mais également à favoriser des relations sexuelles satisfaisantes. OBJECTIF: Présenter les résultats d'une technique de McIndoe modifiée à l'égard de la fonction sexuelle, de la profondeur du vagin et des taux de complication chez les patients ayant une agénésie vaginale. MÉTHODOLOGIE: De 2002 à 2010, 23 patientes ayant une agénésie vaginale ont été hospitalisées à la clinique de gynécologie de la faculté de médecine de l'université d'Istanbul, en Turquie, pour subir une reconstruction vaginale. Toutes les patientes ont subi une intervention de McIndoe modifiée. Les chercheurs présentent les résultats à long terme de cette intervention, après une période de suivi de 18 à 118 mois. RÉSULTATS: Le vagin avait une profondeur moyenne de 8,4 cm après l'opération, variant de 6 cm à 11 cm chez les 19 patientes qui utilisaient le moule régulièrement. Chez les 14 patientes qui utilisaient le moule régulièrement et avaient des partenaires, une seule a ressenti des douleurs marquées pendant les relations sexuelles, et 13 ont déclaré avoir des relations sexuelles satisfaisantes associées à des douleurs légères, sinon inexistantes, et à une bonne sensibilité muqueuse. Par contre, deux des trois patientes qui n'utilisaient pas le moule régulièrement ont ressenti des douleurs marquées pendant les relations sexuelles, et leur vagin avait une profondeur moyenne de 6 cm (plage de 4 cm à 8 cm). CONCLUSION: D'après les observations, la technique de McIndoe modifiée est une intervention simple et efficace pour traiter l'agénésie vaginale, mais une bonne utilisation des moules après l'opération demeure la pierre angulaire du traitement.

Evaluation of ovarian reserve in infertile patients.

Diminished ovarian reserve is a more common occurrence as more women postpone childbearing in modern societies due to social and demographic trends. Diminished ovarian reserve is one of the primary reasons for poor ART outcome. Due to high costs, side effects and heavy burden on patients on ART treatments, patient selection and counseling for prognosis is an important aspect before starting ART. Proper prediction of ovarian reserve before initiation of the treatment can decrease cycle cancellations, help clinicians to establish alternative treatment options (i.e.oocyte donation) for poor prognosis patients. However, indicators of ovarian reserve are not fully successful in predicting the outcome of the treatment. In this review, our aim was to discuss the efficacy of ovarian reserve tests on predicting poor ovarian response and treatment outcome in ART patients.