EVALUATION OF PREIMPLANTATION GENETIC ANEUPLOIDY SCREENING CASES AT A REFERENCE GENETICS CENTER: 10 YEARS' EXPERIENCE.

The aim of this study is to review and evaluate our preimplantation genetic screening (PGS) records in terms of their demographic data, indications, cytogenetic results, pregnancy outcomes and discuss these findings in different aspects. PGS was performed in a total of 84 couples (87 cycles) between the period 2005 to 2015. Biopsied blastomeres from embryos on day 3 were fixed and fluorescence in situ hybridization was carried out for chromosomes 13, 16, 18, 21, 22, X and Y depending on the indication. The diagnostic and clinical data were retrospectively evaluated. A total of 450 blastomeres were biopsied. Ninety-eight of them were found to be suitable for transfer. They were transferred to 72 patients in 75 cycles resulting in 23 pregnancies and 20 healthy births. The most common indication was unexplained infertility. The implantation rate was calculated as 23.4% whereas the take-home baby rate was 26.6% per transfer. The highest rate of healthy living births is achieved in patients having low grade maternal mosaic sex chromosomal aneuploidy. All living births achieved by PGS had normal chromosomal structure which we can propose it as an alternative test for couples at risk to select normal embryos to improve the outcomes of assisted reproductive procedures and to avoid the transfer of chromosomally unbalanced and multiple embryos.

Altered Stem Cell Receptor Activity in the Ovarian Surface Epithelium by Exogenous Zinc and/or Progesterone.

BACKGROUND: Ovarian surface epithelium (OSE) has the characteristics of a stem cell and the potential for differentiation. Previous studies on this subject have succeeded in deriving oocytes from OSE stem cells, leading to the belief that OSE could be used for infertility treatment. METHODS: Each rat (n = 10) was subjected to zinc and/or progesterone injection for 5 days after conception. After a 6-day implantation period, ovarian tissues were removed and comprehensive immunohistochemical analysis of stem cell markers was conducted: Sox2, Klf4, Oct3/4, c-Myc, CD117, CD90, SSEA-1 and Notch pathway analysis; Notch1, Jagged1, and Delta1 in the OSE and ovarian stromal cells were evaluated after treatment with zinc, progesterone, or both. RESULTS: Progesterone moderately affected Sox2 expression (p < 0.001), while zinc application strongly affected Klf4 and Oct3/4 and immunoreactivity (p < 0.001). CD90 immunoreactivity was decreased in the OSE and stroma of the progesterone group (p = 0.006) compared with the zinc (p = 0.244) and zinc/progesterone groups (p = 0.910). On the other hand, SSEA-1 showed moderate staining in the OSE and weak staining in stromal cells in animals treated with zinc (p = 0.727), progesterone (p = 0.626), and zinc/progesterone (p = 0.371), with no differences compared with control. Zinc application affected Notch pathway immunoreactivity, with a significant increase in Notch1 (p = 0.0015) and Jagged1 (p < 0.001). CONCLUSIONS: The expression of putative stem cell markers in the OSE was verified and stem cell receptor activity was raised in the OSE and ovarian stromal cells by zinc and progesterone. Thus, this increased expression allows the therapeutic use of zinc and progesterone in ovary-related infertility and brings a different perspective to reproductive medicine.

Cytogenetic abnormalities in 179 cases with male infertility in Western Region of Turkey: report and review.

PURPOSE: In this study we aimed to evaluate the postnatally screened karyotype results in couples who were referred because of primary infertility between 2000 and 2006 in Izmir. METHODS: The records of a total of 179 cases were evaluated retrospectively. RESULTS: A total of 21 cases (11.74%) showed chromosomal alteration. Thirteen (7.26%) were 47,XXY; three (1.68%) were pericentric inversion of chromosome 9; one (0.56%) 46,XY/45,XO; one (0.56%) 46,XY/47,XXY/48,XXXY; one (0.56%) 46,XY,t(X;1); one (0.56%) 46,XY/46,XY,del(Y)(q11.2) and one (0.56%) 46,XX. CONCLUSIONS: The rate of gonosomal chromosomal abnormalities was nearly three times higher in our region than the rate in the literature. Chromosomal analysis is strongly suggested particularly in those who suffer fertility problems.

Laparoscopic resection or sonography-guided vaginal aspiration of endometriomas prior to ICSI-ET does not worsen treatment outcomes.

OBJECTIVE: To evaluate the effect of the management modality of ovarian endometriomas on ovarian response to COH (controlled ovarian hyperstimulation) and ART (assisted reproductive technology) treatment outcome. DESIGN: Retrospective case control study. SETTING: Ege University Infertility-Family Planning Research and Treatment Center. PATIENTS: 115 cycles of 84 patients who underwent ICSI-ET (intracytoplasmic sperm injection-embryo transfer) with ejaculated sperm were enrolled in the study. The endometrioma resection group (Group I) was comprised of 36 cycles in 29 patients who were treated with laparoscopic endometrioma cyst resection prior to treatment; endometrioma aspiration (Group II) was comprised of 26 cycles in 15 patients whose endometriomas were aspirated prior to treatment; and the control group (Group III) was comprised of 53 cycles in 40 patients for whom the only infertility cause was the tubal factor. INTERVENTIONS: ICSI-ET treatment, laparascopic ovarian endometrioma cyst resection, transvaginal ultrasonography-guided endometrioma cyst aspiration. MAIN OUTCOMES MEASURES: COH results and ICSI-ET treatment outcomes. RESULTS: The groups were similar in all characteristics except for the mean age of the patients in group II being older than those in group I. Gonadotropin consumption was higher, peak estradiol level lower, and the number of oocytes less in the laparascopic resection group (Group I) with respect to the control group. The number of follicles was lower in the cyst aspiration group (Group II) with respect to the control group. The number of follicles larger than 15 mm, number of metaphase II oocytes, the fertilization, pregnancy and implantation rates were similar in all three groups. CONCLUSION: Interventions (laparascopic endometrioma resection, transvaginal ultrasound-guided endometrioma cyst aspiration) performed on endometriomas prior to ART treatment do not worsen the treatment outcome.

The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study.

BACKGROUND: The effect of recombinant human LH (r-hLH; lutropin alfa) in women undergoing controlled ovarian stimulation with recombinant human FSH (r-hFSH) prior to IVF was investigated. METHODS: After down-regulation with the GnRH agonist, buserelin, 114 normo-ovulatory women (aged 18-37 years) received r-hFSH alone until the lead follicle reached a diameter of 14 mm. Patients were then randomized in a double-blind fashion to receive r-hFSH in addition to r-hLH, 75 IU s.c., or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF. The primary end-point was the number of metaphase II oocytes. RESULTS: There were no significant differences between treatment groups for the primary end-point. Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone (P = 0.0001), but there were no significant differences between the groups in dose and duration of r-hFSH treatment required, oocyte maturation, fertilization rate, pregnancy rate and live birth rate. CONCLUSION: In this patient population, the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points.

Screening of Y chromosome microdeletion which contains AZF regions in 71 Turkish azoospermic men.

Screening of Y chromosome microdeletion which contains AZF regions in 71 turkish azoospermic men: In 71 Turkish men Y chromosome microdeletions have been studied before intracytoplasmic sperm injection (ICSI). DNA samples were amplified with 18 STS primers of the azoospermia factor (AZF) region on the Y chromosome by using multiplex polymerase chain reaction (PCR). Microdeletions were detected in 4 azoospermic men (5.6 %); one with a deletion in the AZFb region, while the 3 others had a large deletion extending over multiple chromosomal regions (AZFb+c+d and AZFa+b+c+d). In the patients with microdeletion, no spermatogenetic activity could be detected in testis biopsies. This result confirms the idea that Y chromosome microdeletion analysis is important in investigating the possibility of finding sperm in testicular sperm extraction (TESE). Therefore, we point out the importance of genetic testing and counselling regarding Y chromosome microdeletion for couples requesting ICSI.

Complete down-regulation is not mandatory for good assisted reproductive treatment cycle outcomes.

OBJECTIVE: To determine the implications and predictive value of estradiol concentrations following pituitary down-regulation with gonadotrophin releasing hormone agonists in women undergoing controlled ovarian hyperstimulation for assisted reproductive technology. STUDY DESIGN: A total of 277 patients undergoing ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI) were enrolled into the study and the patients were divided into four groups according to estradiol levels on the initial day of stimulation of which group-A consisted of the patients who had < or =25 pg/ml (n=90), group-B with levels between 26 and 50 pg/ml (n=104), group-C with levels between 51 and 75 pg/ml (n=67) and group-D with levels > or =76-90 pg/ml (n=16) and the results were compared. The primary outcome measures included ovarian response and the clinical pregnancy rates. RESULTS: The clinical pregnancy rates in groups-A, B, C and D were 33.3% (30/90), 26.0% (27/104), 35.8% (24/67), and 25.0% (4/16), respectively, and there was no statistically significant difference (P=0.482). The mean number of oocytes retrieved in groups were (9.7+/-5.8, 10.3+/-6.5, 11.0+/-6.8, and 12.1+/-6.6), respectively (P=0.453) and the fertilization rates in groups-A, B, C and D were found to be similar (75, 80, 73 and 79%, respectively; P=0.658). CONCLUSION: Complete and deep desensitization obviously seems not to be mandatory for successful stimulation in assisted reproductive technology cycles.

Relationship of follicle number, serum estradiol level, and other factors to clinical pregnancy rate in gonadotropin-induced intrauterine insemination cycles.

OBJECTIVE: To determine the characteristics associated with clinical pregnancy rate after gonadotropin-induced intrauterine insemination cycles in patients without male or tubal factor infertility. MATERIALS AND METHODS: One hundred and eighty patients undergoing controlled ovarian hyperstimulation followed by intrauterine insemination were included in the study retrospectively. The patients' files were retrospectively evaluated with respect to age, number of follicles, endometrial thickness and serum hormone levels at baseline and at the day of human chorionic gonadotropin (hCG) administration. The patients with male or unilateral tubal factor infertility were excluded from the study. RESULTS: The serum estradiol level at the day of hCG administration was not correlated with the clinical pregnancy rate (r=-0.05, p=0.481). The number of follicles was not correlated with the clinical pregnancy rate (r=-0.09, p=0.209). There was no significant difference between the clinically pregnants (n=32) and not pregnants (n=148) regarding the mean age, baseline serum levels of luteinizing hormone (LH) and estradiol, serum estradiol and LH levels at the day of hCG administration and endometrial thickness (p>0.05). Although not statistically significant, a pregnancy rate of 14.2% with less than 3 follicles > or = 18 mm is present compared to a pregnancy rate of 27.5% with at least 3 follicles > or = 18 mm and 24% with > or = 4 follicles > or = 18 mm. CONCLUSION: The clinical pregnancy rate does not seem to be affected with the number of follicles present at the time of intrauterine insemination or the serum estradiol level at the day of hCG administration in a controlled ovarian hyperstimulation cycle in non-andrologic and non-peritubal factor infertility; however, there is a clear trend towards higher pregnancy rates with higher number of follicles.

Controlled ovarian hyperstimulation and intrauterine insemination for infertility associated with endometriosis: a retrospective analysis.

OBJECTIVE: To evaluate the efficacy of controlled ovarian hyperstimulation and intrauterine insemination for infertility associated with endometriosis. MATERIAL AND METHODS: A retrospective analysis of 260 patients with the only diagnosis of endometriosis, or male factor, or tubal factor, or unexplained infertility were performed: a total of 56 patients with different stages of endometriosis, a control group consisting of 38 patients with male factor infertility, a group of 26 patients with tubal factor infertility and a group of 140 patients with others (unexplained infertility, ovulation disorders, cervical factor). Pregnancy rate, hormone levels, endometrial thickness and number of follicles were analyzed. RESULTS: Clinical pregnancy rates per patient were similar between endometriosis, male factor, tubal factor, and others including unexplained infertility, ovulation disorders and cervical factor groups (10.7%, 5.4%, 11.5%, 17.9%, respectively; p>0.05). Clinical pregnancy rates per patient were not effected between the 2 subgroups of endometriosis as minimal to mild and moderate to severe [5.1% (2/39) versus 23.5% (4/17), p=0.19]. CONCLUSION: Endometriosis did not affect the clinical pregnancy rate per patient compared to the other infertility factors. Endometriosis of various stages have no effect on the success of controlled ovarian hyperstimulation combined with intrauterine insemination.

Comparison of short and long ovulation induction protocols used in ART applications according to the ovarian response and outcome of pregnancy.

This retrospective study was designed to determine whether there is any difference between short and long protocol ovulation induction with Gonadotropin Releasing Hormone agonist (GnRHa) and gonadotropins used in Assisted Reproductive Technology (ART) applications according to the number of retrieved oocytes, oocyte maturity, fertilization rates, embryo quality and the outcome of pregnancies. 240 cycles consisting of in vitro fertilization (IVF) cycles without andrologic factor and intracytoplasmic sperm injection (ICSI) cycles were evaluated. 112 cycles which were induced by short protocol GnRHa and Follicle Stimulating Hormone (FSH) + Human Menopausal Gonadotropin (HMG) combinations and 128 cycles which were induced by long protocol GnRHa and FSH + HMG combinations were compared according to the number of retrieved oocytes, cancellation rate of cycles, oocyte maturity, fertilization rates, embryo quality and pregnancy rates. The cancellation rate for short protocol cycles were found to be significantly higher than those with long protocol. The number of retrieved oocytes, mature oocytes and fertilized oocytes were also found significantly lower. The quality of embryos did not show any significant difference between these groups. The clinical pregnancy rates were evidently found to be high in the long protocol cycles. As a conclusion we have found that while the number of retrieved oocytes, mature oocytes, fertilized oocytes and clinical pregnancy rates were increasing, the cancellation rate of cycles were decreasing significantly in ART cycles induced by long protocol.

Unilateral ectopic twin pregnancy following an IVF cycle.

We report here a 37-year-old woman who underwent ovulation induction and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment because of infertility who developed vaginal bleeding at the 6th week of gestation. Abdominal ultrasonography was insufficient to distinguish the intrauterine gestational sac. Subsequently, vaginal doppler ultrasonography detected two separate unilateral twin ectopic pregnancies with cardiac activity in both fetuses, which were operated on pelviscopically.

Bilateral jugular venous thromboembolism and pulmonary emboli in a patient with severe ovarian hyperstimulation syndrome.

We report here a case of severe ovarian hyperstimulation syndrome with massive ascites in a 25-year-old woman with a history of primary infertility after an IVF-ET cycle. At the 9th gestational week she presented with neck pain and dyspnea and duplex Doppler sonographic examination of the neck veins revealed bilateral jugular venous thrombosis. Despite prompt administration of low-molecular weight heparin, pulmonary emboli developed a few days later.

Successful pregnancy in an infertile woman with endometrial hyperplasia and embryo transfer. A case report.

BACKGROUND: Successful pregnancy in a woman with complex endometrial hyperplasia with atypia was treated conservatively with gestagens. CASE: The patient was initially diagnosed with complex hyperplasia of the endometrium with atypia by endometrial curettage and treated with several cycles of different gestagens. After repeated endometrial curettage, in vitro fertilization and embryo transfer were introduced for immediate treatment of the patient's infertility in order to avoid the risk of recurrent hyperplasia of the endometrium from estrogens. A single pregnancy was achieved after transfer of embryos obtained from intracytoplasmic sperm injection. This was performed due to poor semen characteristics. The patient delivered a normal, healthy male infant at term. CONCLUSION: Conservative treatment of complex endometrial hyperplasia with atypia in young women wishing to preserve fertility should be considered in carefully selected cases.

Value of serum CA-125 concentrations as predictors of pregnancy in assisted reproduction cycles.

The means by which endometrial receptivity influences conception rates in assisted reproductive technology (ART) is poorly understood. As the glycoprotein CA-125 is a product of human endometrium and is measurable in the peripheral circulation, it was investigated whether it might serve as an indicator of endometrial receptivity and predictor of pregnancy. In this prospective study, serum CA-125 concentrations of 75 ART cycles were measured 1 day before and on the day of human chorionic gonadotrophin (HCG) administration, and on the day of oocyte retrieval. These women did not have endometriosis and were induced by long-protocol gonadotrophin-releasing hormone analogue. Pregnancy was achieved in 35 (46.7%) cycles, but not in 40 cycles (53.3%). Serum CA-125 concentrations 1 day before and on the day of HCG administration and on the day of oocyte retrieval were significantly higher in cycles with pregnancy than in those without pregnancy (P < 0.05). It was noted that CA-125 concentrations on the day of oocyte retrieval were the best predictors of pregnancy, with concentrations >10 IU/ml having an accuracy of 86.6% for pregnancy. In conclusion, in intracytoplasmic sperm injection cycles, women with high serum CA-125 concentrations (>10 IU/ml) on the day of oocyte retrieval had very high pregnancy rates.

Do analogues of gonadotrophin releasing hormone influence follicular fluid steroid levels, oocyte maturity and fertilization rates?

One-hundred-and-twelve samples of follicular fluid from 32 patients undergoing in-vitro fertilization and embryo transfer were analysed in this study. The follicular fluids were analysed for any relationships between oestradiol, progesterone and 17 alpha-hydroxyprogesterone levels, the progesterone/oestradiol and 17 alpha-hydroxyprogesterone/oestradiol ratios and oocyte maturity and fertilization rates. In Group A, consisting of women who used analogues of gonadotrophin-releasing hormone during ovarian stimulation with human menopausal gonadotrophin, the progesterone/oestradiol ratio rose in parallel with the fertilization rate (P less than 0.05). Group B comprised patients treated with human menopausal gonadotrophin alone. No significant relationship was found between the other parameters, oocyte maturation and fertilization rates in either group.

[Lupus anticoagulant and antiphospholipid antibody values in a family with systemic lupus erythematosus]. / Lupus-Antikoagulans- (LA-) und antiphospholipide Antikörper- (APA-) Werte bei einer Familie mit systemischem Lupus erythematodes (SLE).

The Lupus Anticoagulant (LA) is an immunoglobulin directed towards the phospholipid portion of the prothrombin activator complex. This immunoglobulin because first identified in the plasma of patients with Systemic Lupus Erythematodes, was named as Lupus Anticoagulant. Although initially described in patients with SLE, it was subsequently observed in other diseases and also in patients without any manifest disease. SLE or similar diseases are present in 35% of LA (+) patients. The LA prevalence in SLE patients has been found as 34% whereas ACA prevalence was found as 44%. While searching for the presence of LA and the levels of APA in cases having unexplained recurrent fetal losses, a family (a mother and 3 daughters) was discovered, whose each member has been diagnosed as SLE at different times and with different symptoms. Data suggesting the presence of LA and high APA levels were determined in all the members of the family and also it was realised that cause who had recurrent fetal losses had the highest APA levels. In addition to immunoassay methods to detect APA, examination of coagulation tests in patients with unexplained thrombosis and/or fetal losses, would be of great help.

[The experimental mouse model in building an in vitro fertilization center]. / Das Versuchstiermodell der Maus beim Aufbau eines IVF-Zentrums.

Experimental studies on animal models are necessary for the maintenance of practice and experience on IVF and ET, before starting an IVF program. Only so the handling skill of gametes zygote and human embryo culture can be improved. We have started for this reason with IVF on mouse oocytes of CB6F1 Han hybrid strains and used modified Ham's F-10 with 0.75 BSA as culture medium. Until December 1988, 3652 oocytes were collected by the superovulation of 178 oocyte donor mice. The fertilization rate was 67.94%. After the transfer of 62 hybrid embryos obtained from 4 other oocyte donor mice to 4 Balb/c recipient females, 1 recipient mouse delivered 10 living hybrid mice.

[Incidence of intra-abdominal adhesions following pelviscopy and laparotomy]. / Häufigkeit intraabdominaler Adhäsionen nach Pelviskopie und Laparotomie.

In 500 non-selected conservative pelviscopic operations the incidence of the presence of intraabdominal adhesions were compared in patients having had no previous operations, those having had a previous pelviscopy, those having had a previous pelviscopy and laparotomy, and those having had a previous laparotomy alone. The group of patients having undergone no previous operations were found to have the least amount of adhesions followed by those having undergone pelviscopy alone. The highest percentage of intraabdominal adhesions were found in the group of patients having undergone a previous laparotomy. This was also true for patients having undergone a previous pelviscopy and laparotomy. The rate of endometriosis and PID however, in this group was much lower than that of the group having undergone pelviscopy alone. Operative procedures having an equal efficacy whether performed per pelviscopy or laparotomy should therefore be performed per pelviscopy in order to reduce operative trauma and the subsequent post operative formation of adhesions.