Foad Azem

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.

Human embryonic stem cells carrying mutations for severe genetic disorders

Human embryonic stem cells (HESCs) carrying specific mutations potentially provide a valuable tool for studying genetic disorders in humans. One preferable approach for obtaining these cell lines is by deriving them from affected preimplantation genetically diagnosed embryos. These unique cells are especially important for modeling human genetic disorders for which there are no adequate research models. They can be further used to gain new insights into developmentally regulated events that occur during human embryo development and that are responsible for the manifestation of genetically inherited disorders. They also have great value for the exploration of new therapeutic protocols, including gene-therapy-based treatments and disease-oriented drug screening and discovery. Here, we report the establishment of 15 different mutant human embryonic stem cell lines derived from genetically affected embryos, all donated by couples undergoing preimplantation genetic diagnosis in our in vitro fertilization unit. For further information regarding access to HESC lines from our repository, for research purposes, please email dalitb@tasmc.health.gov.il.

Follicular fluid levels of anti-Mullerian hormone as a predictor of oocyte maturation, fertilization rate, and embryonic development in patients with polycystic ovary syndrome.

OBJECTIVEnTo test whether the follicular fluid (FF) concentration of anti-Mullerian hormone (AMH) is associated with oocyte maturation, fertilization rate, and embryonic development in patients with polycystic ovary syndrome (PCOS) undergoing IVF.nnnDESIGNnProspective.nnnSETTINGnAcademic assisted reproductive technology program.nnnPATIENT(S)nTwenty-two samples of FF from 11 patients with PCOS who underwent IVF/ET were analyzed for AMH levels (group A). Twelve women with normal ovulatory cycles served as a control group (group B). The oocytes and preembryos were closely followed until ET.nnnMETHOD(S)nFF was obtained at oocyte retrieval for IVF/intracytoplasmic sperm injection. AMH levels were studied using immunoenzymometric assay.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nFF, AMH levels, oocyte maturation, fertility rate, and embryonic cleavage rate.nnnRESULT(S)nThe mean FF AMH level was 57.3 +/- 79.5 pmol/mL in group A, compared with 70 +/- 120.14 pmol/mL in group B. In group A, the mean AMH level of good-quality embryos was 37.4 +/- 23.4 pmol/mL, compared with 61.9 +/- 102 pmol/mL in a the poor-quality subgroup. No significant correlation was observed between FF AMH levels and oocyte maturation, fertilization, or cleavage rate.nnnCONCLUSION(S)nThis study suggests that there is an association between FF AMH levels and the quality of embryos in patients with PCOS. However, owing to large variance and the number of participants, no statistical significance was reached. The degree of maturation of retrieved oocytes, as well as the success of fertilization, was not found to correlate with FF AMH.

Assessment of ovarian reserve following ovarian tissue banking and/or GnRH-a co-treatment prior to chemotherapy in patients with Hodgkin’s disease

PurposeTo examine ovarian reserve following chemotherapy in women with Hodgkin’s disease.MethodsThe study included nine patients who underwent ovarian tissue cryopreservation (OTCP) prior to chemotherapy consisting of the ABVD regimen (Adriamycin, bleomycin, vinblastine, and dacarbazine) and co-treatment with gonadotropin-releasing hormone agonist (GnRH-a) (Group A), and 13 patients treated by the ABVD protocol only without GnRH-a (Group B). The average age was 25.2u2009±u20092.7xa0years for the women in Group A and 31.8u2009±u20096.8xa0years for those in Group B.ResultsSix months following the end of chemotherapy, the menstrual cycle resumed in all Group A patients and in four Group B patients who had amenorrhea. Eight Group B patients had regular menses during and after chemotherapy. None of the patients suffered from ovarian failure. Two Group A patients conceived in the first year after completing chemotherapy.ConclusionsCo-treatment with GnRH-a has little effect on ovarian protection in women with Hodgkin’s disease.

GnRH-agonist induced depressive and anxiety symptoms during in vitro fertilization–embryo transfer cycles

To determine whether the use of a GnRH agonist inducing a hypogonadic state during IVF-ET cycles induces negative mood symptoms, we conducted a prospective randomized study in 108 women comparing two different controlled ovarian stimulation protocols. A significant phase effect was observed for depression and anxiety symptoms during IVF-ET cycles reflecting an increase in symptoms between the hypogonadal phase and the peak in gonadotropin stimulation; however, the hypogonadal phase induced by the GnRH agonist was not associated with a significant increase in any of the studied mood parameters.

Gonadal steroids and affective symptoms during in vitro fertilization: Implication for reproductive mood disorders

Gonadal steroids (GSs) have been associated with the onset of a number of reproductive-related mood disorders in women, in which fluctuating or unstable hormonal levels are postulated to act as the trigger for the destabilization of mood. There is, however, rather limited direct clinical evidence that can link rapidly changing GS levels with the induction of mood symptoms. We aimed to study the effect of controlled and rapid GS fluctuations on mood in an in vivo model. Women undergoing in vitro fertilization (n=108) were assessed for depression and anxiety levels on 3 time points: during a low estradiol and progesterone baseline, during a gonadotropin stimulated estradiol-dominant phase, and after embryo transfer, during a progesterone-dominant low estrogen phase. Plasma levels for estrogen and progesterone were drawn on these time points. Symptoms of depression and anxiety significantly increased from baseline to the high estradiol levels but were not correlated with estrogen. The sharp drop from high estradiol levels at the estradiol-dominant phase to low levels at the progesterone-dominant phase was significantly correlated with rising depression scores. The rise in progesterone levels from low levels at the estradiol-dominant phase to high levels at the progesterone-dominant phase was significantly and inversely correlated with depression scores. This study suggests that the mechanism underlying the role of estrogen in reproductive-related mood disorders involves an abrupt and precipitous drop in its plasma level that can precipitate negative mood states. This finding has implications on the treatment of GS-related mood disorders.

Preimplantation genetic diagnosis for fragile X syndrome: is there increased transmission of abnormal FMR1 alleles among female heterozygotes?

Fragile X syndrome is caused by a CGG triplet‐repeat expansion mutation in the FMR1 gene. Previous studies have shown increased transmission of abnormal alleles in the 51–60 repeat range. This study was undertaken to evaluate the performance of preimplantation genetic diagnosis (PGD) for fragile X, and to assess the transmission rate of the abnormal FMR1 alleles in this setting.

Women's psychological profile and psychiatric diagnoses and the outcome of in vitro fertilization: is there an association?

The influence of psychological processes and psychiatric syndromes on the outcome of fertility treatments is not well understood. In this prospective study, we investigated the effect of baseline psychiatric diagnosis and situational psychiatric symptoms on several biological outcome factors of in vitro fertilization treatments (IVF). Women undergoing their first IVF treatment (nu2009=u2009108) were interviewed before treatment for the presence of a lifetime DSM-IV-TR disorder. Questionnaires measuring state depression (Center for Epidemiologic Studies Depression scale), anxiety (State Trait Anxiety Inventory), and psychiatric symptomatology (Brief Symptom Inventory) were administered at ovulation induction. Outcome variables were number of retrieved and fertilized oocytes, chemical pregnancy, and a take home baby. Situational anxiety, depression, or other psychiatric symptoms had no effect on any of the outcome measures. Women diagnosed with mood or anxiety disorder prior to the onset of the IVF treatment showed a higher, though not statistically significant, pregnancy success rate compared to women without a diagnosis (57xa0% compared to 38xa0%). We speculate that in women with such psychopathology, chronic stress results in biological effects that impede successful implantation, thus impairing fertility. Fertility treatment using the IVF paradigm may bypass this negative effect, resulting in high success rates. This hypothesis should be further explored.

A second thought on second look laparotomy

Between 1982 and 1987, 43 patients with epithelial ovarian carcinoma, identified as International Federation of Gynaecology and Obstetrics Stages I‐IV, underwent second‐look laparotomy as a part of their treatment protocol. Twenty‐nine patients (67%) had no evidence of residual disease, five (11.6%) had residual disease 1 cm, and nine patients (20%) had residual disease 1 cm at re‐exploration. Persistent disease at the second operation was positively correlated with the initial clinical stage, and negatively correlated with the extent of the original cytoreductive surgery. Fifteen of 29 patients with negative findings (52%) developed recurrent disease within two years. All recurrences were limited to the abdominal cavity only. Three and five years survival, for the patients with negative findings, was 62% and 48% respectively. No documented benefit to the patients could be demonstrated by adopting second‐look laparotomy as a routine procedure in the management of patients with epithelial ovarian carcinoma. In view of our data, as well as that of others, such operations cannot be considered a valuable routine procedure. At this point, second‐look laparotomy may have a role in evaluating the efficacy of a post‐surgical new chemotherapy treatment regimen.

The psychological profile and affective response of women diagnosed with unexplained infertility undergoing in vitro fertilization

It has been hypothesized that unexplained infertility may be related to specific personality and coping styles. We studied two groups of women with explained infertility (EIF, nu2009=u200963) and unexplained infertility (UIF, nu2009=u200942) undergoing an in vitro fertilization (IVF) cycle. Women completed personality and coping style questionnaires prior to the onset of the cycle, and state depression and anxiety scales before and at two additional time points during the cycle. Almost no in-between group differences were found at any of the measured time points in regards to the Minnesota Multiphasic Personality Inventory-2 validity and clinical scales, Illness Cognitions and Life Orientation Test, or for the situational measures. The few differences found suggest a more adaptive, better coping, and functioning defensive system in women with EIF. In conclusion, we did not find any clinically significant personality differences or differences in depression or anxiety levels between women with EIF and UIF during an IVF cycle. Minor differences found are probably a reaction to the ambiguous medical situation with its uncertain prognosis, amplifying certain traits which are not specific to one psychological structure but rather to the common experience shared by the group. The results of this study do not support the possibility that personality traits are involved in the pathophysiology of unexplained infertility.