The association between leptin, adiponectin levels and the ovarian reserve in women of reproductive age.

Background: Reproduction ability requires a certain amount of body fat that is necessary for ovulation, menstruation and pregnancy. Fat tissue represents an endocrine organ with high metabolic activity as it produces adipokines such as leptin and adiponectin. Our aim is to examine potential associations between women of reproductive age's ovarian reserves and their levels of leptin and adiponectin. Method: 74 women between 19 and 40 years of age consented to take part. Based on the patterns of their ovarian reserves, the women were divided into three main groups: women with adequate ovarian reserves (AOR - Group A, n=30), women with polycystic ovary syndrome (PCOS - Group B, n=31) and women with depleted ovarian reserves (DOR - Group C, n=13). Among these groups, several biochemical and demographic parameters were statistically compared. Results: Compared to the other two groups, women with DOR had statistically higher age and follicle stimulation hormone (FSH) levels. For estradiol (E2) and thyroid-stimulating hormone (TSH), no statistically significant difference was seen between the groups. In addition, women with PCOS had higher body mass index (BMI), luteinizing hormone (LH), total testosterone (TT), 17 hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), anti-Mullerian hormone (AMH), and antral follicle count (AFC) than the other two groups. In line with expectations, women with DOR also had lower levels of AMH and AFC than the other two groups. Women with PCOS had higher leptin levels than the other two groups, but there was no statistically significant difference. Women with PCOS had lower levels of adiponectin than the other groups, however the difference was not statistically significant. Conclusion: The way we classified women in our study according to their ovarian reserves is completely consistent with what has been published internationally. The ovarian reserve in women of reproductive age is not strongly correlated with leptin and adiponectin levels. For safe conclusions, more research including a greater number of samples is required.

Effects of Serum Estradiol on Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Lipid Profiles in Women Undergoing In Vitro Fertilization.

BACKGROUND: The mechanisms underlying the impact of estradiol (E2) on low-density lipoprotein cholesterol (LDL-C) levels are not completely understood, although a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) has been proposed. We aimed to investigate the association between levels of E2, PCSK9, and lipid parameters in premenopausal women undergoing in vitro fertilization (IVF). METHODS: Healthy women undergoing IVF in the Department of Obstetrics and Gynecology of the University General Hospital of Ioannina were recruited. Their levels of E2, PCSK9, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides (TGs) were measured 10 days after ovarian depression (E2min) and 7 days after ovarian stimulation (E2max). RESULTS: We included 34 consecutive women of median age 38 (interquartile range 26-46) years who underwent a full IVF cycle. As expected, E2 levels increased by 329.6% from E2min to E2max (108 [47-346] to 464 [241-2471] pg/mL, p < 0.05). During the same time, serum PCSK9 levels decreased by 30.8% (245 ± 80 to 170 ± 64 ng/mL, p < 0.05). TC, LDL-C, and TGs decreased by 0.4%, 3.8%, and 2.2%, respectively, while HDL-C levels increased by 5.3% (all p = NS). CONCLUSIONS: The rise in endogenous E2 during an IVF cycle was related with a significant decline in serum PCSK9 levels, but no significant change in plasma lipids during a 7-day period.

Methotrexate treatment of very high ß-HCG ectopic pregnancy on previous cesarean scar: A case report.

Ectopic pregnancy in a previous caesarean scar is a rare, potentially life-threatening situation that can cause massive bleeding and uterine rupture. Clinical symptoms can range from vaginal bleeding with or without pain, to uterine rupture with hypovolemic shock. Early diagnosis is possible by ultrasound examination, and it is very important because it leads to prompt management, improving maternal morbidity and mortality as well as future fertility. The current case report refers to a G3P2 woman with a history of 2 previous caesarean deliveries, who was diagnosed with an ectopic pregnancy on the caesarean scar using ultrasonography. The patient was treated with methotrexate both systemic and into the sac, as well as with injection into the sac of 5mEq potassium chloride. The woman was followed up until measurements of serum ß-Human Chorionic Gonadotropin were within nonpregnant levels. There is no clear-cut best way to handle cesarean scar pregnancy. Pregnancy with a cesarean scar should be identified and treated as soon as possible in order to avoid serious problems and preserve fertility. However, even more advanced cesarean scar pregnancies can be managed conservatively at first, when a highly expertized team in a tertiary hospital is available.

Is There an Association Between Circulating Kisspeptin Levels and Ovarian Reserve in Women of Reproductive Age?

BACKGROUND/AIM: To investigate the possible association of kisspeptin levels with the ovarian reserves of women of reproductive age. PATIENTS AND METHODS: Eighty women aged 19-40 participated after signing an informed consent. Of these, 74 were finally included as in 6 women the blood samples were considered inappropriate due to hemolysis. They were divided into three main groups according to their ovarian reserve patterns: women with adequate ovarian reserves (Group A - AOR) (n=30), women with increased ovarian reserves (Group B - PCOS) (n=31), and women with diminished ovarian reserves (Group C - DOR) (n=13). RESULTS: Women with diminished ovarian reserves had statistically significantly increased age and FSH compared to the other two groups. No statistically significant difference was found between the three groups for estradiol and thyroid stimulating hormone. Moreover, body mass index, luteinizing hormone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone, anti-Mullerian hormone (AMH), and antral follicle count (AFC) were increased in group B compared to the other two groups. AMH and AFC were decreased in women with diminished ovarian reserves compared to the other two groups, as expected. The comparison of kisspeptin levels between the three groups showed that kisspeptin levels were increased in women with diminished ovarian reserves, compared to the other two groups, but without a statistically significant difference. However, kisspeptin levels in group C were statistically significantly higher than those in group A. CONCLUSION: There are no strong indications that kisspeptin levels are associated with the ovarian reserve in women of reproductive age.

Is Hysteroscopy Prior to IVF Associated with an Increased Probability of Live Births in Patients with Normal Transvaginal Scan Findings after Their First Failed IVF Trial?

(1) Background: Nowadays, pregnancy can be achieved by in vitro fertilisation (IVF) or by intracytoplasmic sperm injection (ICSI) for many infertile couples. However, implantation failure still remains a significant problem and it can be stressful for both patients and doctors. One of the key players for pregnancy achievement is the uterine environment. Hysteroscopy is the most reliable method to evaluate the uterine cavity and to identify any intauterine pathology. The aim of this retrospective study was to compare live birth ranges in between women who after a first failed IVF/ICSI attempt underwent a hysteroscopy and those who were evaluated by a transvaginal scan. (2) The retrospective study took place at the Assisted Reproductive Unit of the University Hospital of Ioannina, Greece, from 2017 to 2020. It included 334 women with normal findings in a repeat ultrasound scan after a failed IVF/ICSI trial, 137 of whom underwent in turn diagnostic hysteroscopy before the next IVF/ICSI. (3) Results: Live birth rates were higher in the study group (58/137 vs. 52/197 p = 0.0025). Abnormal endometrial findings were identified in 30% of the patients of the study group. (4) Conclusions: The addition of hysteroscopy as an additional investigation to those patients with a first failed IVF/ICSI could improve the rates of live births. A properly conducted RCT could lead to a robust answer.

Prenatal Diagnosis of Fetal Jejunal Atresia: A Case Report.

Intestinal atresia is the result of fetal bowel maldevelopment which leads to congenital bowel obstruction. It is a common cause of ileus of the newborn and can occur at any site of the gastrointestinal tract. Prenatal diagnosis relies on the demonstration of dilated loops of the fetal bowel and the presence of polyhydramnios at the end of the second or more frequently the third trimester of pregnancy. This condition requires surgical correction soon after birth, with timely diagnosis improving the prognosis. Here, we present the case of a fetus diagnosed with jejunal atresia at 33weeks of pregnancy.

Neonatal Bowel Obstruction by Pseudolymphoma: A Case Report.

Interstitial obstruction in newborn infants can be caused by several factors such as malrotation, meconium plug syndrome, meconium ileus, Hirschsprung's disease, atresia and stenosis. Neonates who have been diagnosed with an interstitial obstruction are in need of immediate treatment; otherwise, they can deteriorate rapidly. Surgery remains the mainstay of treatment in most cases. Pediatric gastrointestinal tumours are very rare, especially in newborn infants. Their management is usually different as compared to adults. We present the case of a newborn infant who was born with interstitial obstruction. At the 31 weeks scan, a significant dilation of the small bowel was observed and the diagnosis of interstitial obstruction was made. When born, the newborn was transferred to a specialised unit and underwent a laparotomy. The findings were consistent with a tumour causing the obstruction; the histology reported this tumour as benign lymphoid hyperplasia. Pseudolymphoma is a very rare cause of fetal interstitial obstruction, and it should be considered in the differential diagnosis.

Ultralong administration of gonadotropin-releasing hormone agonists before in vitro fertilization improves fertilization rate but not clinical pregnancy rate in women with mild endometriosis: a prospective, randomized, controlled trial.

OBJECTIVE: To evaluate the effects of gonadotropin-releasing hormone agonists (GnRH-a) on fertility in women with mild endometriosis who are undergoing in vitro fertilization and embryo transfer (IVF-ET) procedures. DESIGN: Prospective, randomized, controlled trial. SETTING: Three tertiary university hospitals. PATIENT(S): Four hundred infertile women with mild endometriosis, documented with laparoscopy, undergoing IVF and 200 women with tubal factor infertility. INTERVENTION(S): Administration of GnRH-a for 3 months before an IVF attempt (group A, n = 200) or IVF without GnRH-a (group B, n = 200). MAIN OUTCOME MEASURE(S): Follicular fluid (FF) levels of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8, and IL-1 receptor antagonist; fertilization rate (FR), implantation rate (IR), quality of embryos, and clinical pregnancy rate (PR). RESULT(S): Women who received GnRH-a had a statistically significantly reduced concentration of FF cytokines compared with women who did not receive this regimen. Women in group B had a reduced FR (61.7; 95% CI, 59.20-64.20) compared with the women in group A (72.7; 95% CI, 70.50-74.90) and compared with the women with tubal factor infertility (74.7; 95% CI, 72.00-77.24). The embryo quality, IR, and clinical PR showed no statistically significant improvement in the women of group A compared with group B. CONCLUSION(S): Women who received GnRH-a for 3 months had a lower concentration of FF cytokines. These women had also a higher FR than the women who did not receive GnRH-a. However, the IR, embryo quality, and clinical PR showed no statistically significant difference when comparing the two groups. CLINICALTRIALS. GOV ID: NCT01269125.

Pharmacological preconditioning for short-term ex vivo expansion of human umbilical cord blood hematopoietic stem cells by filgrastim.

Although umbilical cord blood (UCB) hematopoietic stem cell transplantation (UCBT) has emerged as a promising haematological reconstitution therapy for leukemias and other related disorders, the insufficient UCB stem cell dosage still hinders better clinical outcomes. Previous research efforts, by focusing on ex vivo UCB expansion capabilities have sought to benefit from well-known mechanisms of self-renewal characteristics of UCB stem cells. However, the long-term (> 21 days) in vitro culture period and the low neutrophil recovery significantly reduce the transplantability of such ex vivo expanded UCB stem cells. To overcome the latter hurdles in this study, a post-thaw, short-term ex vivo expansion methodology of UCB mononuclear (UCB-MN) and CD34(+) cells has been established. Notably, such effort was achieved through pharmacological preconditioned of UCB cultures by filgrastim agent already used in the clinical setting. In crucial cell populations implicated in the promotion of functional engraftment, the progression of free survival rates (PFS), a marked increase of 6.65 to 9.34 fold for UCB-MN and 35 to 49 fold for CD34(+) cells has been noticed. Overall, these results indicate that transplantation of pharmacologically-preconditioned ex vivo expansion of UCB stem and progenitor cells keep high promise upon transplantation to enhance therapeutic potential in everyday clinical practice.

Ascites in the Puerperium in the Context of a Woman with Turner Syndrome Who Conceived through Assisted Reproductive Technology.

The case is about a young female who delivered twins by caesarean section (CS). On the 4th postoperative day, she presented with ascites which was resistant to empirical antibiotic and diuretic treatment. The woman was affected by Turner syndrome (TS); she had a medical background of chronic use of hormonal medication since puberty and conceived through ART- (assisted reproduction techniques-) IVF-oocyte donation. It is important to exhibit high suspicion for clot formation in the hepatic vasculature during the puerperium, especially in the case of history of chronic hormone treatment. Ascites albumin gradient and Doppler values lead to the diagnosis of thrombosis and the administration of high doses of anticoagulants is considered to be fundamental.

Dehydroepiandrosterone administration before IVF in poor responders: a prospective cohort study.

The use of dehydroepiandrosterone (DHEA) may improve ovarian stimulation outcomes in women of advanced reproductive age and could reduce embryo aneuploidy. In this prospective study, 48 women diagnosed with poor ovarian response received DHEA supplementation for at least 12 weeks. These women were compared with a group of poor responders (n = 113) who did not receive supplementation. During the study period, patients taking day 2 FSH and oestradiol were measured monthly before and after treatment. Stimulation characteristics, stimulation outcome and clinical outcome (clinical pregnancy and live birth rates) were reported. Evaluation of anti-Müllerian hormone (AMH) was carried out before initiation of treatment and immediately before the subsequent stimulation. Supplementation with DHEA for at least 12 weeks resulted in a modest, but statistically significant, increase in AMH levels and decrease in baseline FSH (P < 0.001 and P = 0.007, respectively). Administration of DHEA had no effect on any of the stimulation parameters nor was there any difference in clinical pregnancy rates and live birth rates between the two groups. Supplementation with DHEA significantly affects women with poor prognosis undergoing ovarian stimulation for IVF. Patients should be counselled about the uncertain effectiveness, potential side-effects and cost of this treatment.

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

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.

The follicular outcome after standard gonadotropin stimulation is associated with ERα and ERß genotypes.

The aim is to study the association of estrogen receptor α (ERα) and estrogen receptor ß (ERß) gene polymorphisms and diplotypes with ovarian response to follicle-stimulating hormone (FSH) stimulation and the hormone levels [FSH, luteinizing hormone (LH), E2] at the third day of the menstrual cycle. Three hundred women undergoing medically assisted reproduction and 300 women with at least one spontaneous pregnancy participated in the study. ERα PvuII and XbaI polymorphisms as well as ERß AluI polymorphism were genotyped. The FSH, LH, and E2 levels were determined at the third day of the menstrual cycle, while the follicular size, the follicle, and oocyte numbers were recorded during oocyte retrieval. PvuII CC, XbaI GG, and AluI GG women were characterized by increased amounts of large follicles compared to PvuII TT, XbaI AA, and AluI AA women (p = 0.045, 0.01, and 0.033, respectively). The PvuII CC/XbaI GG diplotype was also significantly associated with higher large follicle numbers compared to the PvuII TT/XbaI AA diplotype (p = 0.024). However, no associations were observed between ER gene polymorphisms and the hormonal profile, the follicle/oocyte numbers, and the pregnancy rates. ERα and ERß genetic variants were associated with ovarian response to standard gonadotropin stimulation of women undergoing in-vitro fertilization affecting mainly the follicular growth.

Influence of FSHR diplotypes on ovarian response to standard gonadotropin stimulation for IVF/ICSI.

OBJECTIVE: To explore the association of FSHR 307 (T/A)/FSHR 680(N/S) diplotypes with ovarian response to follicle stimulating hormone (FSH) stimulation of women undergoing medically assisted reproduction (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). STUDY DESIGN: The study population consisted of 304 women undergoing IVF/ICSI and 300 women with at least 1 spontaneous pregnancy as controls. FSHR polymorphisms were genotyped. Controlled ovarian stimulation and IVF/ICSI were performed in the 304 couples. During oocyte retrieval the follicular size, the follicle and oocyte numbers were recorded. Serum FSH, luteinizing hormone and estradiol were determined at the third day of the menstrual cycle. RESULTS: The FSHR 307(T/A)/FSHR 680(N/S) diplotype analysis revealed lower serum FSH levels, higher follicle and oocyte numbers, increased numbers of large follicles as well as decreased empty follicle numbers in Thr307Thr/Asn680Asn women as compared to Thr307 Ala/Asn680Ser and Ala307Ala/Ser680Ser women (p < 0.006, p < 0.01, p < 0.008, p < 0.01, p < 0.005, respectively). CONCLUSION: FSHR diplotypes were significantly associated with ovarian response to gonadotropin stimulation. FSHR diplotype analysis could be informative for ovarian stimulation outcome and the selection of the proper stimulation protocol, which would ensure a sufficient number of mature oocytes for IVF/ICSI.

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.

CYP19 gene variants affect the assisted reproduction outcome of women with polycystic ovary syndrome.

OBJECTIVE: Cytochrome P450 aromatase catalyzes the irreversible transformation of androgens into estrogens. The association of CYP19(TTTA)n polymorphism with the hormonal profile and the assisted reproduction outcome of women with polycystic ovary syndrome (PCOS) was explored. METHODS: One hundred and thirty-two women with PCOS and 200 with male-factor infertility, as controls, participated in the current study. The CYP19(TTTA)n polymorphism was genotyped, while the hormonal profile was determined at the third day of the menstrual cycle. During oocyte retrieval, the follicular size, the follicle and oocyte numbers were recorded. RESULTS: Genotype analysis revealed 6 CYP19(TTTA)n alleles with 7-12 repeats. In PCOS women, the CYP19(TTTA)7 allele presence was associated with lower serum E2 levels at the third day of the menstrual cycle (p < 0.009), lower large follicle (p < 0.02) and total oocyte numbers (p = 0.006), but with significantly higher pregnancy rates after assisted reproduction (p < 0.004). CONCLUSIONS: Potential associations of the CYP19(TTTA)7 allele with ovarian response to standard gonadotrophin stimulation and with assisted reproduction outcome were found in PCOS women, probably due to androgen/estrogen ratio alterations.

The ovarian response to standard gonadotrophin stimulation depends on FSHR, SHBG and CYP19 gene synergism.

PURPOSE: Follicle stimulating hormone, sex hormone-binding globulin and cytochrome P450 aromatase play crucial roles in the regulation of mammalian reproduction. The synergistic effect of FSHR 307(T/A)/FSHR 680(N/S), SHBG(TAAAA) ( n ) and CYP19(TTTA) ( n ) genotypes on ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction (IVF/ICSI) was explored. METHODS: The study population consisted of 300 women under IVF/ICSI treatment and 300 women with at least with at least one successful child birth as controls. The polymorphisms were genotyped while the follicular size, the follicle and oocyte numbers were recorded during oocyte retrieval. RESULTS: The genotype analysis, excluding heterozygotes for each particular polymorphism, revealed eight combined homozygotic FSHR/SHBG/CYP19 genotypes. A gradual reduction in the number of follicles and oocytes from FSHR 307Thr/680Asn allele/long SHBG allele/long CYP19 allele homozygotes to FSHR 307Ala/680Ser allele/short SHBG allele/short CYP19 allele homozygotes was observed (20.36 ± 6.74 vs. 8.05 ± 2.47, p < 0.008 and 13 ± 4.63 vs. 6.1 ± 2.32, p < 0.02, respectively). CONCLUSIONS: FSHR/SHBG/CYP19 combined genotypes are associated with ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction.

Phosphatidylethanolamine N-methyltransferase and choline dehydrogenase gene polymorphisms are associated with human sperm concentration.

Choline is a crucial factor in the regulation of sperm membrane structure and fluidity, and this nutrient plays an important role in the maturation and fertilizing capacity of spermatozoa. Transcripts of phosphatidylethanolamine N-methyltransferase (PEMT) and choline dehydrogenase (CHDH), two basic enzymes of choline metabolism, have been observed in the human testis, demonstrating their gene expression in this tissue. In the present study, we explored the contribution of the PEMT and CHDH gene variants to sperm parameters. Two hundred oligospermic and 250 normozoospermic men were recruited. DNA was extracted from the spermatozoa, and the PEMT -774G>C and CHDH +432G>T polymorphisms were genotyped. The genotype distribution of the PEMT -774G>C polymorphism did not differ between oligospermic and normozoospermic men. In contrast, in the case of the CHDH +432G>T polymorphism, oligospermic men presented the CHDH 432G/G genotype more frequently than normozoospermic men (62% vs. 42%, P<0.001). The PEMT 774G/G genotype was associated with a higher sperm concentration compared to the PEMT 774G/C and 774C/C genotypes in oligospermic men (12.5 ± 5.6 × 10(6) spermatozoa ml(-1) vs. 8.3 ± 5.2 × 10(6) spermatozoa ml(-1), P<0.002) and normozoospermic men (81.5 ± 55.6 × 10(6) vs. 68.1 ± 44.5 × 10(6) spermatozoa ml(-1), P<0.006). In addition, the CHDH 432G/G genotype was associated with higher sperm concentration compared to CHDH 432G/T and 432T/T genotypes in oligospermic (11.8 ± 5.1 × 10(6) vs. 7.8 ± 5.3 × 10(6) spermatozoa ml(-1), P<0.003) and normozoospermic men (98.6 ± 62.2 × 10(6) vs. 58.8 ± 33.6 × 10(6) spermatozoa ml(-1), P<0.001). In our series, the PEMT -774G>C and CHDH +432G>T polymorphisms were associated with sperm concentration. This finding suggests a possible influence of these genes on sperm quality.

Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation.

PURPOSE: The association of cytochrome P450 aromatase gene CYP19(TTTA) ( n ) polymorphism with ovarian response to FSH stimulation was explored. METHODS: Three hundred women undergoing medically assisted reproduction and 300 women with at least one spontaneous pregnancy participated in the study. CYP19(TTTA) ( n ) polymorphism was genotyped, while serum hormones were determined. During oocyte retrieval, the follicular size, the follicle and oocyte numbers were recorded. RESULTS: Six CYP19(TTTA) ( n ) alleles with 7 to 12 repeats were revealed. Women homozygous for long CYP19(TTTA) ( n ) alleles presented with lower serum FSH levels at the third day of the menstrual cycle (p < 0.001) and higher large follicle numbers (p < 0.01), compared to women homozygous for short CYP19(TTTA) ( n ) alleles. The CYP19(TTTA) ( 7 ) allele was associated with higher serum FSH levels (p < 0.003), with lower total follicle (p < 0.02) and large follicle numbers (p < 0.03), while CYP19(TTTA) ( 7 ) allele-carriers presented more frequently with small follicles than CYP19(TTTA) ( 7 ) allele-non carriers (p < 0.01). CONCLUSIONS: CYP19 genetic variants were associated with ovarian reserve and response to standard gonadotrophin stimulation of women undergoing in vitro fertilization.

Association of TNFα, TNFR1, and TNFR2 polymorphisms with sperm concentration and motility.

Tumor necrosis factor α (TNFα) is a multifunctional cytokine that regulates various cellular processes related to spermatogenesis. Two types of cell receptors, TNFR1 and TNFR2, mediate TNFα activity. In the present study, we sought to explore the association of TNFα -857C→T, TNFR1 36A→G, and TNFR2 676T→G polymorphisms with sperm concentration and motility. Two hundred ninety men were examined during infertility investigation; of those, 170 men were normozoospermic and 120 were oligospermic. Polymerase chain reaction analysis revealed significant differences in genotype distribution of the TNFR1 36A→G polymorphism between normozoospermic and oligospermic men. Men with oligozoospermia presented TNFR1 36A/A genotypes less frequently than normozoospermic men (P < .001). The presence of the TNFR1 36G allele was significantly increased in oligospermic men (P < .001). Furthermore, the presence of the TNFR1 36G allele was associated with lower sperm concentration in normozoospermic men (P < .03) and in the total study population (P < .001), and with lower sperm motility in normozoospermic men (P < .007) and in the total study population (P < .001). No significant associations were found between TNFα -857C→T and TNFR2 676T→G polymorphisms and semen quality. The TNFR1 36A allele is associated with increased sperm concentration and motility in our series, supporting the significance of TNFR1 gene in semen quality.