Ioannis P. Kosmas

Elective single embryo transfer

•  Elective single embryo transfer has been implemented in Belgium and Scandinavian countries to decrease the incidence of twin pregnancy and the associated complications. •  The extra cost associated with achieving an equal number of pregnancies through elective single embryo transfer needs to be considered in the context of any additional neonatal care expenses associated with double embryo transfer. •  Acceptable ongoing pregnancy and delivery rates have been obtained when comparing single with double embryo transfer. •  Maternal age, previous attempts, day of embryo transfer and cost should be taken into account.

Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis.

Objective To evaluate whether the C677T polymorphism of the methylenetetrahydofolate reductase (MTHFR) gene is consistently associated with hypertension in pregnancy. Design Meta-analysis of studies comparing women with and without hypertension in pregnancy for the C677T MTHFR polymorphism. Methods Studies were identified with MEDLINE and EMBASE searches complemented with perusal of bibliographies of retrieved articles and communication with investigators. Between-study heterogeneity was estimated and data were combined with random effects models. Sensitivity analyses examined the effect of population and disease characteristics. Bias diagnostics evaluated the evolution of the postulated genetic effect over time and the potential for publication bias. Results Across 23 comparisons (3169 hypertensive women, 3044 controls), having the T allele (TT or CT) increased the odds of hypertensive disease of pregnancy by 1.21-fold (95% confidence interval, 1.01–1.44), but there was large between-study heterogeneity (P = 0.003). The results were similar and heterogeneity persisted when sensitivity analyses were limited to studies of Caucasian populations, or those of patients with significant proteinuria. While patients with diastolic hypertension ⩾ 110 mmHg showed an odds ratio of 1.41 (95% confidence interval, 1.03–1.73), no association was seen in patients with less severe diastolic hypertension (odds ratio, 1.00; 95% confidence interval, 0.61–1.65). Early published studies tended to show stronger associations than the subsequent studies. Conclusions While bias cannot be excluded, the meta-analysis suggests that the T allele may increase the risk of severe diastolic hypertension during pregnancy.

Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation

BackgroundMany factors have been put forward as a driving mechanism of surgery-triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions.MethodsA prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups. Specific traumatic OS conditions were induced by midline incision line (MIL) extension and tissue drying and specific LS conditions were remodelled by intraperitoneal CO2 insufflation at the 10 cm of water. TIR was evaluated at the 24th, 72nd, 120th and 168th hour by scoring scale. Statistical analysis was performed by the non-parametric t test and two-way ANOVA using Bonferroni post-tests.ResultsMore pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p < 0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p < 0.05 at the 24th and 72nd; p < 0.01 - 120th and p < 0.001 - 168th hrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p > 0.05). However larger adhesion size (41.67 ± 33.63) was observed after OS in comparison with LS (20.31 ± 16.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p = 0.03). Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe postoperative adhesions in the OS group than those observed in the LS group.ConclusionsMIL extension and tissue drying seem to be the key factors in the pathogenesis of adhesion formation, triggering severe inflammatory reactions of the peritoneal tissue surrounding the MIL resulting in local and systemic consequences. CO2 insufflation however, led to moderate inflammation and less adhesion formation.

The opioid neuropeptides in uterine fibroid pseudocapsules: a putative association with cervical integrity in human reproduction

Abstract The myoma pseudocapsule (MP) is a fibro-vascular network rich of neurotransmitters, as a neurovascular bundle, surrounding fibroid and separating myoma from myometrium. We investigated the distribution of the opioid neuropeptides, as enkephalin (ENK) and oxytocin (OXT), in the nerve fibers within MP and their possible influence in human reproduction in 57 women. An histological and immunofluorescent staining of OXT and ENK was performed on nerve fibers of MP samples from the fundus, corpus and isthmian-cervical regions, with a successive morphometric quantification of OXT and ENK. None of the nerve fibers in the uterine fundus and corpus MPs contained ENK and the nerve fibers in the isthmian–cervical region demonstrated an ENK value of up to 94 ± 0.7 CU. A comparatively lower number of OXT-positive nerve fibers were found in the fundal MP (6.3 ± 0.8 CU). OXT-positive nerve fibers with OXT were marginally increased in corporal MP (15.0 ± 1.4 CU) and were substantially higher in the isthmian–cervical region MP (72.1 ± 5.1 CU) (p < 0.01). The distribution of OXY neurofibers showed a slight into the uterine corpus, while are highly present into the cervico-isthmic area, with influence on reproductive system and sexual disorders manifesting after surgical procedures on the cervix.

Semen quality is influenced by androgen receptor and aromatase gene synergism

STUDY QUESTION Does synergism between AR(CAG)(n) and CYP19(TTTA)(n) polymorphisms influence the quality of sperm? SUMMARY ANSWER AR(CAG)(n) and CYP19(TTTA)(n) polymorphisms had a synergistic effect on sperm concentration and motility. WHAT IS KNOWN ALREADY Androgens exert their action in the testicular tissue by binding to androgen receptor (AR), while their action is mediated by the aromatase P450 enzyme (CYP19). AR(CAG)(n) alleles are associated with sperm motility and CYP19(TTTA)(n) allelic variants have implications for sperm concentration and motility. STUDY DESIGN, SIZE, DURATION Two hundred oligozoospermic and 250 normozoospermic men who presented for infertility investigation were examined during a period of 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS Conventional semen analysis was performed. DNA was extracted from spermatozoa and both polymorphisms were genotyped by polymerase chain reaction. Serum hormone levels were determined. MAIN RESULTS AND THE ROLE OF CHANCE Six combined genotypes were identified between the 18 AR(CAG)(n) alleles with 12-32 repeats and the 6 CYP19(TTTA)(n) alleles with 7-12 repeats. A gradual reduction in the sperm concentration (10(6)/ml) and motility (%) from long AR allele-non-CYP19(TTTA)(7) allele carriers to long AR allele-CYP19(TTTA)(7) homozygotes and from short AR allele-non-CYP19(TTTA)(7) carriers to short AR allele-CYP19(TTTA)(7) homozygotes was observed in normozoospermic men (means ± SD; concentration: 93 ± 53.1 versus 65 ± 48.6 and 85 ± 60.1 versus 37 ± 17.2l, P < 0.002; motility: 63 ± 10.3 versus 55 ± 14.5 and 52 ± 19.6 versus 41 ± 13.7, P < 0.001, respectively). Similar associations were observed in oligozoospermic men (concentration: 10 ± 4.2 versus 9 ± 5.9 and 10 ± 6.3 versus 6 ± 3.1, P < 0.03; motility: 47 ± 17.1 versus 39 ± 6.2 and 39 ± 22 versus 27 ± 18.3, P < 0.003, respectively). The above associations of the combined genotypes with sperm concentration and motility were confirmed in the total study population (P < 0.006 and P < 0.001, respectively). LIMITATIONS, REASONS FOR CAUTION Our study population was limited to Greek Caucasian adult males, residents of Northwest Greece. WIDER IMPLICATIONS OF THE FINDINGS The confirmation of our findings in other populations would verify the significance of AR and CYP19 genes for spermatogenesis. STUDY FUNDING/COMPETING INTERESTS This study did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. The authors declare no conflicts of interest.

Successful term pregnancy after treatment of a cesarean scar ectopic gestation by endoscopic technique and conservative therapy

OBJECTIVE To describe a case of cesarean scar pregnancy treated successfully by endoscopic technique and medical therapy. DESIGN Case report. SETTING State general hospital in a major city. PATIENT(S) A 32-year-old woman with two cesarean sections and a recent curettage presented with ectopic cesarean scar pregnancy. INTERVENTION(S) Transvaginal ultrasound and hysteroscopy were used for diagnosis, and conservative therapy with methotrexate and hysteroscopy to treat the patient. MAIN OUTCOME MEASURE(S) Modified hysteroscopic technique and outcome. RESULT(S) Sonography and hysteroscopy revealed the presence of a gestational sac in the lower segment of the uterus in a patient with a cesarean section scar. She was successfully treated with systemic methotrexate and aspiration of the sac and local methotrexate injection under endoscopic control. CONCLUSION(S) Endoscopic intervention combined with medical treatment can result in a good therapeutic outcome with preservation of fertility in early ectopic cesarean scar pregnancy.

A Combined Ultrasound and Histologic Approach for Analysis of Uterine Fibroid Pseudocapsule Thickness

Authors investigated 75 patients with uterine myomas, appraising whether fibroid pseudocapsule (FP) thickness varies depending on fibroid location, by a prospective cohort trial (level of evidence II-2) settled in University-affiliated Hospitals. Uteri were scanned via bidimensional and power Doppler ultrasound (US) to map the fibroids and record the FP thickness, prior to hysterectomy for symptomatic uterine fibroids. After hysterectomy, FP specimens were sampled and analyzed by pathologists. Ultrasound and histology data were matched. Pseudocapsule thickness of 108 fibroids was measured: subserosal fibroids (SSFs), intramural fibroids (IMFs), and fibroids near the endometrial cavity (FEC). The FEC’s pseudocapsules were considerably thicker than those of IMF and SSF measured by US and histology (P = .001). A clear cutoff existed between FEC pseudocapsule thickness and all other pseudocapsules, with significant differences observed at 2 mm (P = .001). Similarity between histological and US measurements was observed only with IMF pseudocapsules, whereas FEC or SSF showed significant differences. The pseudocapsule of fibroids is considerably thicker near the endometrial cavity when compared to those of both IMFs and SSFs. Since fibroids closest to the endometrial cavity are the most involved in fertility and infertility and FP is considerably thicker near the endometrial cavity, it is possible to hypothesize an involvement of FP of fibroid near the endometrium since FP contains many neuropeptides and neurotransmitters that are physiologically active, even if these data may take on a broader meaning in a study on a larger number of patients.

Ovarian hyperstimulation syndrome inhibition by targeting VEGF, COX-2 and Calcium pathways: a preclinical randomized study

Abstract Objective: The efficacy of vascular endothelial growth factor (VEGF), COX-2, calcium and aromatase inhibitors in an ovarian hyperstimulation syndrome (OHSS) rat model was tested. Methods: One hundred and eight female Wistar rats were randomly divided in nine groups. The control group received saline, while the OHSS group received rec-FSH for 4 consecutive days. The other seven groups received rec-FSH (4d) and Bevacizumab twice, Parecoxib daily, Verapamil daily, Parecoxib daily and Bevacizumab twice, Verapamil daily and Bevacizumab twice, Parecoxib and Verapamil daily, Letrozole and Meloxicam daily, respectively. All groups received also hCG at the 5th day. Results: All intervention groups were characterized by reduced vascular permeability compared to the OHSS group, which in the groups of Verapamil (Calcium inhibition) and Parecoxib + Verapamil (COX-2 + Calcium inhibition) presented significant statistical difference. The Verapamil group showed the lowest corpus luteum formation, while the Parecoxib (COX-2 inhibition), the Parecoxib + Verapamil (COX-2 + Calcium inhibition), the Bevacizumab + Parecoxib (VEGF + COX-2 inhibition) and the Bevacizumab + Verapamil (VEGF + Calcium inhibition) groups were also characterized by lower corpus luteum numbers compared to the OHSS group. Furthermore, lower graafian follicle formation was observed in the above groups, while the ovarian weight and the hormonal profile were not significantly affected. Conclusions: Studying the different check points of the VEGF pathway, we conclude that targeting calcium pathways could be beneficial for the vascular permeability control in an OHSS animal model. Chinese abstract 目的：检测血管内皮生长因子（VEGF）、COX-2、钙和芳香化酶抑制剂对卵巢过度刺激综合征（OHSS）大鼠模型的效果。 方法：108只雌性Wistar大鼠随机分成9组。对照组用生理盐水处理、而卵巢过度刺激综合征组用重组-FSH连续用药4天。另外7组分别用4天重组-FSH和两次贝伐单抗；每日帕瑞昔布钠；每日维拉帕米；每日帕瑞昔布钠和两次维拉帕米；每日维拉帕米和两次贝伐单抗；每日帕瑞昔布钠和维拉帕米；每日来曲唑和美洛昔康处理。全部9组在第5天用人绒毛膜促性腺激素处理。 结果：对比卵巢过度刺激综合征组，所有干预组均有血管通透性降低的特征，其中维拉帕米组（钙离子拮抗制）和帕瑞昔布钠+维拉帕米组（COX-2+钙离子拮抗剂）有显著的统计学差异。相比OHSS组，维拉帕米组黄体形成数最少，而帕瑞昔布钠组（COX-2拮抗剂）、帕瑞昔布钠+维拉帕米组（COX-2+钙离子拮抗剂）、帕瑞昔布钠+贝伐单抗组（VEGF+COX-2拮抗剂）和贝伐单抗+维拉帕米（VEGF+钙离子拮抗剂）组也有较少黄体数。此外，以上各组中，形成成熟卵泡的数目也较少，而卵巢重量和激素受到的影响并不明显。 结论：通过研究不同的VEGF通路的检测点，我们得出以下结论：在卵巢过度刺激综合征的动物模型中，钙信号通路可能对控制血管通透性有益。

A surgical polypragmasy: Koninckx PR, Corona R, Timmerman D, Verguts J, Adamyan L. Peritoneal full-conditioning reduces postoperative adhesions and pain: a randomised controlled trial in deep endometriosis surgery. J Ovarian Res. 2013 Dec 11;6(1):90

A surgical polypragmasy: Koninckx PR, Corona R, Timmerman D, Verguts J, Adamyan L. Peritoneal full-conditioning reduces postoperative adhesions and pain: a randomised controlled trial in deep endometriosis surgery. J Ovarian Res. 2013 Dec 11;6(1):90 Ospan A Mynbaev, Peter Biro, Marina Yu Eliseeva, Andrea Tinelli, Antonio Malvasi, Ioannis P Kosmas, Mykhailo V Medvediev, Tatiana I Babenko, Madina I Mazitova, Sergei S Simakov and Michael Stark

Sperm flow cytometric parameters are associated with ICSI outcome

The association of sperm nuclear chromatin condensation and ploidy with embryo development and outcome after intracytoplasmic sperm injection (ICSI) was explored. The study population consisted of 16 couples referred to Ioannina University Medical School In vitro Fertilization Unit with male factor infertility and serious impairments in sperm nuclear chromatin condensation and ploidy, according to sperm flow cytometry. Additionally, 20 couples with male factor infertility and relatively high sperm flow cytometry parameters participated as controls. The 35 cycles of the study population were characterized by a lower fertilization rate (P<0.001) as well as decreased grade A embryo rate (P=0.004) and increased grade C embryo rate (P=0.028), compared with the 29 cycles of the control group. Additionally, a significantly elevated arrested embryo rate (P<0.001) and a decreased clinical pregnancy rate (P<0.020) were observed in the couples of the study population. Consequently, high levels of sperm nuclear chromatin condensation abnormalities and sperm aneuploidies are probably associated with lower fertilization rates, impaired embryo quality, elevated arrested embryo rates and decreased pregnancy rates. These preliminary results strongly support the use of sperm flow cytometry as a potential prognostic tool of ICSI outcome.