Prophylactic SSRI treatment for women suffering from mood and anxiety symptoms undergoing in vitro fertilization-a prospective placebo-controlled study.

To explore the mood protective effect of prophylactic SSRI treatment on women undergoing IVF suffering from moderate affective and anxiety symptoms. In a randomized double blind, placebo-controlled, parallel design study, 41 women diagnosed with an Adjustment Disorder, who were undergoing IVF treatments, were randomized into two groups; a study group (n = 22) administered escitalopram 10 mg/day, and a control group (n = 19) administered placebo for a total of 8 weeks before and during the IVF treatment cycle. Patients were assessed at the onset of drug treatment and at embryo transfer. The main outcome measure was the difference in mean score severity rating of depression and anxiety symptoms on the CES-D and Zung questionnaires between groups at the time of embryo transfer. Secondary outcome measures included the MHI rating subscales addressing aspects of psychological distress and coping. At the day of embryo transfer (6 weeks of drug treatment), the CES-D average score for the treatment group was 6.40 (6.71) and 27.47 (4.29) on the Zung Self-Rating Anxiety Scale, while the placebo group scored an average of 15.83 (8.69) and 33.17 (6.95) receptively. These findings were significant (p = .004, p = .015 receptively) and were endorsed by the scoring on the MHI questionnaire subscales. Short-term treatment with SSRI may serve as a prophylactic treatment against the perpetuation and possible worsening of depressive and anxiety symptoms in women undergoing IVF treatments. Further studies concerning pharmacological interventions in larger samples and studies addressing screening for psychological stress indicators in this population are warranted.

Improving preimplantation genetic diagnosis (PGD) reliability by selection of sperm donor with the most informative haplotype.

BACKGROUND: The study is aimed to describe a novel strategy that increases the accuracy and reliability of PGD in patients using sperm donation by pre-selecting the donor whose haplotype does not overlap the carrier's one. METHODS: A panel of 4-9 informative polymorphic markers, flanking the mutation in carriers of autosomal dominant/X-linked disorders, was tested in DNA of sperm donors before PGD. Whenever the lengths of donors' repeats overlapped those of the women, additional donors' DNA samples were analyzed. The donor that demonstrated the minimal overlapping with the patient was selected for IVF. RESULTS: In 8 out of 17 carriers the markers of the initially chosen donors overlapped the patients' alleles and 2-8 additional sperm donors for each patient were haplotyped. The selection of additional sperm donors increased the number of informative markers and reduced misdiagnosis risk from 6.00% ± 7.48 to 0.48% ±0.68. The PGD results were confirmed and no misdiagnosis was detected. CONCLUSIONS: Our study demonstrates that pre-selecting a sperm donor whose haplotype has minimal overlapping with the female's haplotype, is critical for reducing the misdiagnosis risk and ensuring a reliable PGD. This strategy may contribute to prevent the transmission of affected IVF-PGD embryos using a simple and economical procedure. TRIAL REGISTRATION: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. DNA testing of donors was approved by the institutional Helsinki committee (registration number 319-08TLV, 2008). The present study was approved by the institutional Helsinki committee (registration number 0385-13TLV, 2013).

The effect of a germline mutation in the APC gene on ß-catenin in human embryonic stem cells.

BACKGROUND: Most cases of colorectal cancer (CRC) are initiated by inactivation mutations in the APC gene, which is a negative regulator of the Wnt-ß-catenin pathway. Patients with familial adenomatous polyposis (FAP) inherit a germline mutation in one APC allele, and loss of the second allele leads to the development of polyps that will turn malignant if not removed. It is not fully understood which molecular mechanisms are activated by APC loss and when the loss of the second APC allele occurs. METHODS: Two FAP human embryonic stem cell (hESCs) lines were derived from APC mutated embryos following pre-implantation genetic diagnosis (PGD) for FAP. These FAP-hESCs were cultured in vitro and following extended culture: 1) ß-catenin expression was analyzed by Western blot analysis; 2) Wnt-ß-catenin/TCF-mediated transcription luciferase assay was performed; 3) cellular localization of ß-catenin was evaluated by immunoflorecence confocal microscopy; and 4) DNA sequencing of the APC gene was performed. RESULTS: We have established a novel human in-vitro model for studying malignant transformation, using hESCs that carry a germline mutation in the APC gene following PGD for FAP. Extended culturing of FAP1 hESCs led to activation of the Wnt signaling pathway, as demonstrated by enhanced ß-catenin/TCF-mediated activity. Additionally, ß-catenin showed a distinct perinuclear distribution in most (91 %) of the FAP1 hESCs high passage colonies. DNA sequencing of the whole gene detected several polymorphisms in FAP1 hESCs, however, no somatic mutations were discovered in the APC gene. On the other hand, no changes in ß-catenin were detected in the FAP2 hESCs, demonstrating the natural diversity of the human FAP population. CONCLUSIONS: Our results describe the establishment of novel hESC lines from FAP patients with a predisposition for cancer mutation. These cells can be maintained in culture for long periods of time and may serve as a platform for studying the initial molecular and cellular changes that occur during early stages of malignant transformation.

Blastomere biopsy for PGD delays embryo compaction and blastulation: a time-lapse microscopic analysis.

PURPOSE: The purpose of the study was to explore the effect of blastomere biopsy for preimplantation genetic diagnosis (PGD) on the embryos' dynamics, further cleavage, development, and implantation. METHODS: The study group included 366 embryos from all PGD treatments (September 2012 to June 2014) cultured in the EmbryoScope™ time-lapse monitoring system. The control group included all intracytoplasmic sperm injection (ICSI) embryos cultured in EmbryoScope™ until day 5 during the same time period (385 embryos). Time points of key embryonic events were analyzed with an EmbryoViewer™. RESULTS: Most (88 %) of the embryos were biopsied at ≥8 cells. These results summarize the further dynamic development of the largest cohort of biopsied embryos and demonstrate that blastomere biopsy of cleavage-stage embryos significantly delayed compaction and blastulation compared to the control non-biopsied embryos. This delay in preimplanation developmental events also affected postimplantation development as observed when the dynamics of non-implanted embryos (known implantation data (KID) negative) were compared to those of implanted embryos (KID positive). CONCLUSION: Analysis of morphokinetic parameters enabled us to explore how blastomere biopsy interferes with the dynamic sequence of developmental events. Our results show that biopsy delays the compaction and the blastulation of the embryos, leading to a decrease in implantation.

Obstetricians and gynecologists: which characteristics do Israeli lesbians prefer?

AIM: The aim of this study was to explore lesbians' preferences when choosing obstetricians/gynecologists. MATERIAL AND METHODS: This cross-sectional study included 100 lesbian and 100 heterosexual women. A 40-item questionnaire assessed the correlation between a patient's sexual identity and her specific preferences for obstetricians/gynecologists. RESULTS: The top five most important parameters for both groups in choosing obstetricians/gynecologists overlapped greatly. Four of those were experience, ability, knowledge and personality. Only one parameter differed: lesbians ranked 'sexually tolerant' as the third most important characteristic while heterosexuals ranked 'availability' as the fifth most important characteristic. Lesbians rated 'sexual tolerance' significantly higher than heterosexuals (P < 0.001). More lesbians (56%) preferred female obstetricians/gynecologists compared to heterosexuals (21%) (P < 0.001). When compared to heterosexuals, more lesbians preferred female obstetricians/gynecologists for intimate and non-intimate procedures (P < 0.001). But within the lesbian population, a higher percentage of subjects showed a preference for female obstetricians/gynecologists only for intimate procedures. Lesbians used the following to describe their preference for female obstetricians/gynecologists: feeling more comfortable; gentle; sympathetic; patient; more understanding of women's health; better physicians in general; and more sexually tolerant (P < 0.001 vs heterosexual). However, when we looked only at the lesbian population, the majority did not exhibit a preference for a female obstetrician/gynecologist for any of these reasons. The main reason given by the 56% of the lesbians who said they prefer female obstetricians/gynecologists was feeling more comfortable. CONCLUSION: Overwhelmingly lesbians prefer sexually tolerant obstetricians/gynecologists regardless of their gender; however, only a small number of lesbian subjects in this study considered their obstetricians/gynecologists as displaying this characteristic.

Cabergoline for reducing ovarian hyperstimulation syndrome in assisted reproductive technology treatment cycles. A prospective randomized controlled trial.

OBJECTIVE: To investigate whether cabergoline (Cb2), a dopamine agonist, reduces ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing assisted reproductive technology (ART), and to analyze whether cabergoline affects the outcome of ART. STUDY DESIGN: Forty infertile women at risk of developing OHSS were enrolled in the trial. The inclusion criteria were as follows: infertile women undergoing IVF with serum estradiol concentration > 4,000 pg/mL or with > 20 follicles > 12 mm on the day of human chorionic gonadotropin (hCG) administration, and 18-40 years of age. They were randomized into 2 groups: the Cb2 group (n = 20) received 0.5 mg oral Cb2 per day for 8 consecutive days beginning on the day of hCG, and the control group (n = 20) received no medication. RESULTS: Ascites was significantly lower (p = 0.008) in the Cb2 group as compared with the control group. The incidence of moderate OHSS was also significantly lower (p = 0.04) in the Cb2 as compared to the control group. There was no evidence of statistically significant differences regarding the parameters of ART outcome. CONCLUSION: Our data supports the use of Cb2 in the management of high-risk women undergoing ART and, consequently, achieving lowered risk of OHSS, with no deleterious impact on ART outcomes.

Total fertilization failure in intra-cytoplasmic sperm injection cycles--classification and management.

In this retrospective cohort study we intended to propose a classification and preliminary management strategy for couples exhibiting total fertilization failure (TFF) in intra-cytoplasmic sperm injection (ICSI) cycles. Sixteen couples with a total of 27 cycles exhibiting TFF, age <40 and/or more than four M2 oocytes aspirated were enrolled. While TFF occurred in 4.3% of all 3723 ICSI cycles, in women younger than 40 with at least 5 M2 oocytes the TFF rate was 0.7%. Indications for ICSI were severe male factor and unexplained infertility. Of the 16 couples with TFF, 4 demonstrated a single episode of TFF, with either subsequent or former normal fertilizations, thus implying possible sporadic faulty laboratory conditions. Ten couples demonstrated repeated total or very low fertilization rates, hinting at a gamete defect not overcome by ICSI. Two couples experienced TFF in the first and only cycle performed at our unit. We conclude that initial and repeated TFF hints at severe gamete defects for which only donor gametes may prove successful while sporadic TFF events could simply imply a technical modifiable condition.

Embryo quality in controlled ovarian stimulation for in vitro fertilization in young poor responders.

This retrospective matched case control study was conducted to evaluate the effects of poor ovarian response in a group of young women (20-30 years) on embryos quality in controlled ovarian hyperstimulation (COH) for in vitro fertilization. Thirty-nine young patients with poor ovarian response (≤5 oocytes on retrieval) were enrolled and compared to age- and date-matched controls. Maximal Estradiol levels, number of oocytes aspirated, number of M2 oocytes and number of fertilized oocytes were significantly lower in the study group compared to controls. Implantation rate and rate of good quality embryos transferred of the study group and control were comparable (15.3 versus 16.3% and 62 versus 67.2%, respectively). Additionally, clinical pregnancy rate per transfer and delivery rate per transfer were also comparable (26.6 versus 35.8% and 23.3 versus 30.7%, respectively). The rate of cycles with no transfer, however, was 23.07% in the study group compared to zero cycles with no transfer in the control group. We conclude that young poor responders may still have reasonable proportion of good quality embryos when compared to controls. This results in comparable implantation rate and clinical pregnancy rate. Cycle transfer cancelation, however, represents a true barrier for achieving pregnancy.

[Anti mullerian hormone (AMH)--is it a new reliable marker of the ovarian reserve? Its role in predicting the ovarian response in assisted reproductive technology (ART)].

Anti-Müllerian hormone (AMH) is predominantly known for its important role in the differentiation of the male and female sexual system during the early embryonic period. Recently, many animal and human researches have been studying the role of the AMH in the postnatal ovarian function. In the female, AMH is produced by the granulosa cells of early developing follicles. It plays a major role in the folliculogenesis and seems to be able to inhibit the initiation of the growth of primordial follicles and FSH-induced follicles. As AMH is expressed throughout the folliculogenesis, from the primary follicular stage to the antral stage, the serum levels of AMH may represent both the quantity and the quality of ovarian follicles. Thus, the AMH levels may be useful as a new potential marker of the ovarian reserve. As compared to other ovarian reserve tests, the AMH has unique characteristics which make it a favorable marker. The measurement of AMH levels may be useful in the prediction of poor response and cycle cancellation as well as hyper-response and the ovarian hyperstimulation syndrome in assisted reproductive technology (ART). We assume that the measurement of AMH Levels may play a role in the individualization of treatment strategies among patients who are treated by ART. However, the AMH cannot predict the qualitative ovarian response in ART. In men, the AMH was not found to have satisfactory clinical utility as a single marker of spermatogenesis.

Intrafollicular and serum levels of leptin during in vitro fertilization cycles: comparison between the effects of recombinant follicle-stimulating hormones and human menopausal gonadotrophin.

OBJECTIVES: To compare the effect of recombinant follicle-stimulating hormones (r-FSH) and human menopausal gonadotrophin (hMG) on leptin levels in serum and follicular fluid (FF) during in vitro fertilization IVF/ET treatment, and to investigate whether leptin levels in the follicular fluid and/or serum are correlated with IVF success. METHODS: Sixty-three patients undergoing IVF cycle were subdivided into two groups. r-FSH was used to for controlled ovarian hyperstimulation in 29 patients (Group A) while, hMG was used in 34 patients (Group B). Our main outcomes were serum and FF leptin on the day of oocyte collection. RESULT(S): The two groups were comparable in age, body mass index (BMI), indications for IVF/ET, E2 level on human chorionic gonadotrophin day, number of retrieved oocytes, fertilization rate, number of transferred embryos and pregnancy rate. Serum and FF leptin levels were similar between the two study groups. Additionally, no correlation was found between levels of leptin in either serum or FF and cycle results such as: number of retrieved oocytes, fertilization rate and pregnancy rate. CONCLUSIONS: r-FSH and hMG have been found to have comparable effects on leptin levels in the serum and the FF of patients undergoing IVF/ET. Additionally, leptin levels in both serum and FF on day of retrieval have no correlation to IVF/ET outcome.

[Preimplantation genetic diagnosis (PGD) for cancer predisposition syndromes].

INTRODUCTION: Most cases of cancer are sporadic and only 5%-10% are inherited with variable penetrance. Whenever the causative mutation is known, prevention of affected offspring birth may be achieved by prenatal or preimplantation genetic diagnosis (PGD). AIM: To devise a scoring system (SS) that appraises the justification of PGD for each patient and to evaluate the efficacy, reliability and accuracy of PGD for cancer predisposition syndromes in 48 cycles. METHODS: A semi-quantitative SS was developed by evaluating disease characteristics (onset, severity, inheritance pattern and penetrance) and patient clinical variables (infertility, objection to abortion and a need for diagnosis of additional genetic syndrome). PGD cycles were performed by blastomere biopsy of cleavage stage embryos, followed by single cell multiplex nested PCR for the cancer predisposition mutation and flanking polymorphic markers. RESULTS: Seventeen couples referred to PGD for cancer predisposition. According to the devised SS, fourteen were accepted and 3 were declined. Of the 14 accepted couples, 13 had at Least one affected member and 11 couples required IVF anyway. A total of 48 PGD cycles were performed resulting in 8 pregnancies. CONCLUSION: PGD for cancer predisposition genes is a possible and reliable procedure, suitable especiaLly for infertile carrier couples. DISCUSSION AND SUMMARY: The assessment of the characteristics of the cancer syndrome and consideration of the variables of each couple enable, the justified application of PGD procedure. The continuous discovery of cancer predisposition mutations will result in an ever-increasing demand for PGD to prevent the transmission of Lethal mutations to the next generations.

Adverse obstetric outcome for the vanishing twin syndrome.

The aim was to compare obstetric outcomes of IVF singleton pregnancies diagnosed with vanishing twin (VT) syndrome with those pregnancies originating as singleton pregnancies and with twin pregnancies. In this case control study, 57 patients diagnosed with VT syndrome were matched and compared with 171 singleton controls and 171 twin controls. Mean gestational age was 35.1+/-3.7 versus 38.2+/-2.6 weeks (P=0.001) for patients and singleton controls respectively. Birth weights were 2834.4+/-821.2 versus 3036+/-489.3g (P=0.02), proportion of low birth weight (< 2500 g) was 33.3 versus 11.7% (P=0.0001) and very low birth weight (< 1500 g) 3.5 versus 0.6% for patients and singleton controls respectively. The proportion of deliveries before 28 weeks of gestation was 7.0 versus 1.2% (P=0.01) for patients and singleton controls respectively. When comparing the study group to twin control pregnancies, a similar gestational age at delivery (35 weeks) and rate of preterm birth (23%) were found. In conclusion, pregnancies diagnosed with the VT syndrome after IVF carry a higher rate of adverse obstetric outcomes in terms of preterm deliveries and lower birth weight, compared with IVF pregnancies that were originally singleton. Additionally, significant similarities were observed in the obstetrics outcome of vanishing twin pregnancies and twin pregnancies.

Histologic evaluation of fresh human ovarian tissue before cryopreservation.

Transplantation of cryopreserved tissue from patients with cancer may carry the risk of reactivation or redissemination of micrometastases. This prospective study was conducted to evaluate the potential involvement of micrometastases in ovarian tissue in cancer patients. Ovarian biopsies were collected from patients who underwent ovarian tissue cryopreservation, in our IVF unit before chemotherapy between 2000 and 2008. Indications for cryopreservation included breast cancer (n=13), osteosarcoma (n=13), hematologic malignancies (n=13), uterine cervix carcinoma (n=2), endometrial carcinoma (n=1), colon cancer (n=1), and brain medulloblastoma (n=1). The samples were stained with hematoxylin and eosin, and examined histologically. Immunoperoxidase broad-spectrum cytokeratin staining was also performed on specimens from breast cancer patients. There were 44 patients (age range 5-40 yr) who yielded 40 specimens. No gross pathologic involvement was observed, and the histologic examination revealed normal histology with no evidence of metastases. Our findings showed that for the purpose of considering ovarian tissue cryopreservation in cancer patients, the likelihood of microscopic metastases within ovaries of normal appearance is apparently very low. Clarification of the actual risk of ovarian involvement and any subsequent risk of micrometastases and tumor reimplantation requires further investigation.

Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia.

OBJECTIVE: Severe congenital neutropenia is an inherited disease characterized by low peripheral blood neutrophils, amenable to bone marrow transplantation. Genetic analysis in the family here described detected a ELA2 splice-site mutation in the affected child and also in his asymptomatic father. The parents requested preimplantation genetic diagnosis (PGD), coupled with HLA matching, to obtain a suitable bone marrow donor for the affected child. METHODS: A PGD protocol was developed, based on multiplex nested PCR for direct analysis of the ELA2 mutation, flanking polymorphic markers and HLA typing. RESULTS: The amplification efficiency of the mutation was > 90% in single leukocytes from the affected child but only 67% in the father. Analysis of single haploid sperm cells from the father demonstrated three different sperm-cell populations: (1) sperm cells harboring the ELA2 mutation on the 'affected' haplotype, (2) sperm cells without the ELA2 mutation on the 'normal' haplotype, and (3) sperm cells without the ELA2 mutation on the 'affected' haplotype. CONCLUSION: These data demonstrate that the ELA2 mutation in the father occurred de novo during his embryonic development, resulting in somatic as well as germ-line mosaicism. This conclusion was also taken into consideration when PGD was performed.

Clomiphene citrate vs. letrozole for cryopreserved-thawed embryo transfer: a randomized, controlled trial.

OBJECTIVE: To assess the endometrial thickness, hormonal status and pregnancy rates with clomiphene citrate (CC) vs. letrozole in frozen-thawed embryo transfer protocols. STUDY DESIGN: Nineteen patients who had previously undergone in vitro fertilization (IVF) with embryo cryopreservation were prospectively and randomly enrolled in a randomized, controlled trial. Nine patients were treated with CC, 100 mg per day, from day 3 to day 7 of the cycle, and 10 patients were treated with letrozole, 2.5 mg per day, on the same cycle days. beta-Human chorionic gonadotropin (beta-hCG) was administrated when the leading follicular size was > or = 18 mm. Endometrial thickness was measured on cycle day 8, beta-hCG day, transfer day and 7 days after embryo transfer. Estradiol levels were determined on the day of beta-hCG administration. RESULTS: Patients' ages and number of previous unsuccessful IVF cycles were similar between the 2 groups. Endometrial thickness was significantly higher in the letrozole group as compared to the CC group on the day of beta-hCG administration (9.1 +/- 3.6 vs. 6.9 +/- 1.2 mm, p<0.05), on the day of embryo transfer (10 +/- 1.7 vs. 7.6 +/- 1.4 mm, p<0.05) and 7 days after embryo transfer (12.2 +/- 0.4 vs. 9.0 +/- 3.0 mm, p<0.05). Estradiol levels in the letrozole group were significantly lower than in the CC group on the beta-hCG day (231 +/- 132 vs. 515 +/- 363 pg/L, p<0.05). Pregnancy was not achieved in either group. CONCLUSION: Endometrial thickness is improved by letrozole as compared to CC in frozen-thawed embryo transfer cycles. Further investigation is needed to assess pregnancy and implantation rates.

First live birth following IVF-embryo transfer and use of GnRHa alone for ovarian stimulation.

Several case reports have shown that some patients may develop ovarian cysts or ovarian hyperstimulation syndrome following the administration of gonadotrophin-releasing hormone agonist (GnRHa). This is the first report of a live birth following ovarian stimulation and IVF-embryo transfer using sole administration of GnRHa as part of the short protocol. The 31-year-old woman was referred to IVF because of severe male factor. Following spontaneous menses, ovulation induction was started by administering a conventional flare-up regimen (triptorelin 0.1 mg) on day 1 of the cycle. On day 3, the oestradiol concentration was 444 pg/ml and the progesterone concentration was 0.3 ng/ml. On day 4, about 10 follicles, 8-10 mm in size, were detected in each ovary, and the oestradiol concentration rose to 704 pg/ml (progesterone was unchanged). Surprisingly, on day 9, the follicles were 18-19 mm in diameter, oestradiol had increased to 3678 pg/ml and progesterone was now 2.88 ng/ml. Informed consent was obtained for administering human chorionic gonadotrophin and for performing ovum retrieval 36 h later. Nineteen MII oocytes were retrieved, and all were fertilized, yielding high-quality embryos. Two embryos were transferred, and the patient conceived and recently gave birth to a healthy singleton.

Does high serum progesterone level on the day of human chorionic gonadotropin administration affect pregnancy rate after intracytoplasmic sperm injection and embryo transfer?

OBJECTIVE: The present study was conducted to evaluate the effect of serum progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration on embryo quality and pregnancy rate in intracytoplasmic sperm injection (ICSI) cycles. DESIGN AND SETTING: This was a retrospective analysis conducted in the in vitro fertilization (IVF) unit of a tertiary hospital. PATIENTS: Two hundred and one patients who underwent a total of 280 IVF treatment cycles allocated to ICSI during routine IVF/embryo transfer treatment. Results. In cycles with elevated serum P, higher estradiol levels were noted (1915 pg/ml vs. 1256 pg/ml; p<0.05), more oocytes were retrieved and manipulated, and more embryos were available for transfer. Embryo grading was comparable between the two groups. The average age was lower in the group with elevated P; but the pregnancy rate was significantly lower (16.4% vs. 27.6%, p = 0.03). CONCLUSIONS: Our data demonstrate no deleterious effect of elevated P on embryo quality. However, high serum P adversely affects implantation and pregnancy rates.

[The involvement of the zona pellucida in unexplained infertile women].

Unexplained infertility (*UI) was a common problem before the IVF era. A couple was declared as UI only after they passed all the routine common tests and no reason was found for the infertility. The introduction of ICSI in the IVF clinics enabled the investigation of the quality of the couple's gametes. Thus, the definition of the term UI was refined and the number of couples encompassed by this term decreased dramatically. Zona Pellucida (ZP) incompetence was described as one of the causes of UI. We recently (2004) published a case study of an UI couple due to this cause. The oocytes of the woman collapsed during the preparation of the oocytes for sperm injection. These oocytes suffered from irregular ZP and abnormal appearance. Only after gentle treatment of the oocyte-cumulus complex and ICSI fertilization, embryo development and delivery of normal newborn was achieved. This woman and others who suffer from UI did not conceive in a natural way since the ZP of the ovulated eggs did not bind sperm cells and, thereby, were not fertilized. It only recently became possible to find the reason for the infertility of the couple and the solution, through the use of highly advanced technology in the IVF-ICSI process. One of the reasons for the deformatted ZP is the malfunction of the gene that encodes the 4 glycoproteins, which compose the ZP. This is now under investigation in our Institute.

Higher C-reactive protein levels during IVF stimulation are associated with ART failure.

BACKGROUND: C-reactive protein (CRP) is believed to be a sensitive marker of endothelial activation and inflammation. The association between an inflammatory state and CRP has prompted research on changes in CRP levels in assisted reproductive technique (ART) cycles. IVF success and CRP levels were not correlated previously. The aim of this prospective study was to assess CRP levels during IVF stimulation and correlate them with IVF success. MATERIALS AND METHODS: Twenty-eight Women were stimulated using the 'Flare-up' protocol with down-regulation of Triprorelin. CRP levels were measured on cycle days 3, 8, ovum pick-up day and 12 days following embryo-transfer (betahCG testing day). MAIN OUTCOME MEASURES: CRP levels in women who conceived after IVF protocol (n=8) were compared to CRP levels in women who failed to conceive (n=20). RESULTS: The mean age for both groups was similar. CRP levels were significantly different on day 3 (p<0.05), but not on day 8, of the cycle. Average CRP levels on ovum pick-up and on betahCG test days were similar, as was the number of oocytes collected or embryos replaced. Patients who failed to conceive had significantly higher levels of CRP on day 3 of the cycle, before commencement of gonadotrophin administration, and the higher levels continued throughout treatment, although not reaching statistical significance. CONCLUSIONS: An inflammatory state, indicated by high CRP levels during stimulation, may serve as a prognostic indicator of IVF success.

Prolonged activation of the coagulation system during in vitro fertilization cycles.

OBJECTIVE: To investigate coagulation system changes during an in-vitro fertilization (IVF) cycle using Thromboelastogram (TEG) that enables analysis of the elastic properties of whole blood samples and provides a global assessment of the hemostatic function. STUDY DESIGN: A prospective study. TEG indices were evaluated in 23 women who underwent controlled ovarian stimulation for IVF at four points in time: 1. At the beginning of the cycle (corresponding to the lowest levels of E2), 2. On the day of hCG administration (maximal stimulation with highest E2 levels), 3. On the day of ovum pickup and 4. At the first pregnancy test (approximately 14days after ovum pickup). The main outcome measures were TEG indices including R-time (time until initial fibrin formation), K-time (time until a 20mm amplitude is achieved), α angle (the rate of clot formation), Maximum Amplitude (MA, strength of the fibrin clot), Coagulation Index (CI, calculated overall indicator of coagulation) and LY30 (the decrease in graph amplitude). RESULTS: R, K, α angle, MA and CI before hCG administration and at the time of the first pregnancy test were significantly higher compared to the baseline measurement before gonadotropins administration. No correlation was found between E2 and TEG indices. CONCLUSION: Ovarian stimulation is associated with prolonged increased coagulability that extends after the time of maximal ovarian stimulation. The lack of association between E2 levels and TEG indices suggest that additional factors may play a role in the pathogenesis of increased coagulability in women with ovarian stimulation.