Helen Bili

Intracytoplasmic sperm injection. Survey of world results.

Abstract: The widespread application of intracytoplasmic sperm injection (ICSI) has raised concern about the efficacy and safety of this novel technique. The European Society of Human Reproduction and Embryology (ESHRE) has established an ICSI Task Force to collect annually the clinical results, the outcome of pregnancy, and the follow‐up of children after ICSI using ejaculated, epididymal, and testicular sperm in order to address these important issues in a relatively short time. Over a 3‐year span (1993–1995), the number of centers for ICSI increased from 35 to 101, and the total number of ICSI cycles per year rose from 3,157 to 23,932. The incidence of oocytes damaged by the procedure remained low (<10%), whereas the fertilization rates obtained with ejaculated, epididymal, and testicular spermatozoa for 1995 were 64%, 62%, and 52%, respectively. Thus, 86–90% of the couples had embryo transfer, and the viable pregnancy rate was 21% for ejaculated, 22% for epididymal, and 19% for testicular sperm, while the incidence of multiple gestations was 29%, 30%, and 38%, respectively. It is noteworthy that no difference was found in ICSI results concerning the etiology of azoospermia, for example, obstructive (congenital or acquired) or nonobstructive. Furthermore, 3,149 transfers of frozen‐thawed embryos after ICSI with ejaculated, epididymal, or testicular sperm were performed, and in 11%, 9%, and 7% of them, respectively, a viable pregnancy was achieved. The ICSI results were similar during this 3‐year period, irrespective of the origin of the sperm. The perinatal outcome of children born after ICSI was not different from that after in vitro fertilization or natural conception and was only affected by multiplicity. Moreover, the incidence of major or minor malformations was not increased, but the chromosomal, especially the sex chromosomal, aberration rate was slightly elevated (∼2%). Therefore, ICSI has opened new horizons in the treatment of male infertility. The achievement of pregnancy after ICSI using ejaculated, epididymal, or testicular sperm is very satisfactory. The procedure seems to be safe, but further follow‐up of the children is necessary to more accurately assess its safety.

Therapeutic approach of immotile cilia syndrome by intracytoplasmic sperm injection: a case report

OBJECTIVE To present a case of immotile cilia syndrome, a very rare cause of male infertility and to evaluate the role of the recently suggested treatment by intracytoplasmic sperm injection (ICSI). DESIGN Case report. SETTING Tertiary-care academic hospital. PATIENT(S) One man with immotile cilia syndrome, showing no motile spermatozoa despite normal morphology and viability. INTERVENTION(S) The patients partner underwent two cycles with IVF of the oocytes achieved by ICSI. MAIN OUTCOME MEASURE(S) Evaluation of ICSI procedure in cases of immotile cilia syndrome. RESULT(S) Thirty-three percent of the oocytes were fertilized and subsequently divided enabling ET in both cycles. CONCLUSION(S) Intracytoplasmic sperm injection seems to represent a promising approach to the problem of infertility in men with immotile cilia syndrome.

Safety of GnRH agonists and antagonists

The widespread application of protocols using gonadotropin-releasing hormone (GnRH) agonists or antagonists in assisted reproduction treatment has led to an increasing number of pregnancies exposed to these drugs. This issue has raised scepticism as to the safety of these medications, concerning both pregnant women and their offspring. The main parameters that can be studied to ensure the safety of GnRH analogues include: a) systemic and local reactions to the medication; b) incidence of ovarian hyperstimulation syndrome (OHSS); c) direct effect on oocytes and embryos; and d) the health of those children exposed. So far, no systemic side effects and no major local reactions have been reported following the use of GnRH agonists or third-generation antagonists. On the other hand, the incidence of OHSS seems to be higher with GnRH agonist protocols compared to conventional or GnRH antagonist protocols. The recent cloning of the GnRH receptor has led to the demonstration of GnRH receptor gene expression in the human ovary, although the existence of GnRH receptors per se remains controversial. Similarly, the potential direct effect of GnRH analogues on the follicles and oocytes remains a matter of debate. The incidence of miscarriage and the health of children born as a result of in vitro fertilisation (IVF) treatment do not appear to be influenced by the GnRH agonist treatment. This also seems to be the case for the GnRH antagonists, although the available information on this issue is still limited. Therefore, most of the accumulated data concerning the safety of the GnRH analogues are encouraging, and no serious side effects have been reported. On the other hand, as no definite conclusions about the safety of these drugs can be drawn until now, continued assessment of the aforementioned parameters in long-term follow-up studies is recommended.

Cytokines in the human ovary : Presence in follicular fluid and correlation with leukotriene B4

Purpose: This study was undertaken to correlate the follicular levels of interleukin (IL)-1α, IL-2, tumor necrosis factor-α (TNF-α), and leukotriene (LT) B4 with oocyte maturity, fertilization, and achievement of pregnancy.Methods: The material was obtained from 22 women undergoing IVF, 8 of whom became pregnant and 14 of whom did not.Results: All of the studied cytokines and LT B4 were found in follicular fluids, but there were no significant differences according to oocyte maturity, fertilization, embryo quality, and achievement of pregnancy. On the other hand, a significant positive correlation was found between IL-1α and TNF-α, IL-1α, and LT B4 as well as between TNF-α and LT B4 in follicular fluids with subsequently fertilized oocytes.Conclusions: It seems that IL-1α, TNF-α and LT B4 may take part in the process of follicle wall degradation, and their follicular correlations may suggest more optimal follicular and oocyte development and maturation.

Acute renal failure in pregnancy

Between 1982 and 1992, 18 cases of pregnancy-related acute renal failure (PR-ARF) were observed (9% of the total number of ARF). Mean age of the women was 32 years (22-40 years). Uterine hemorrhage and preeclampsia/eclampsia were the major causes of ARF, accounting for 61% of the cases. Patchy renal cortical necrosis was suspected in 2 cases whereas signs of disseminated intravascular coagulation (DIC) or microangiopathic hemolytic anemia were present in 6 (33%) and 9 (50%) cases, respectively. Ten women required hemodialysis; and 6 of them, additional plasma exchange sessions. Five patients (28%) died during the acute phase of the illness, mainly due to brain damage, hepatic failure, and sepsis. Among the survivors, a complete (61.5%) or partial recovery (23.1%) was usually seen, but irreversible renal failure was recorded in 2 cases with postpartum hemolytic uremic syndrome (HUS). Short-lasting oligoanuria (< 3 days) represents a good prognostic index. However, the presence of vascular injury (cortical necrosis, HUS) seems to carry a poor prognosis. In conclusion, PR-ARF is still a critical occurrence, associated with serious prognosis for both women and kidneys. So far, the most effective measures remain the careful prevention and the aggressive management of the obstetric complications.

Outcome of pregnancy in women with glomerular diseases.

Over the last 16 years the evolution of 24 pregnancies in 17 women with biopsy-proven glomerular disease was analyzed. The underlying renal histology was IgA nephropathy in 8 cases, lupus nephritis in 7, mesangiocapillary glomerulonephritis type I in 1, and focal segmental glomerulosclerosis in 1. All but 2 had normal renal function before conception and 3 were hypertensive. Fetal survival rate was 75%. There were 6 preterm deliveries (33.3%), 3 newborns small for gestational age (17%), 1 stillbirth, and 5 therapeutic abortions. The perinatal mortality was 5.5%. De novo hypertension occurred in 8 pregnancies (33.3%). In 11 pregnancies (46%) increased proteinuria was diagnosed and in 6 (25%) a decline in maternal renal function was recorded. Permanent impairment of renal function was seen in 2 women with renal insufficiency before conception. Maternal hypertension and renal function impairment were associated more frequently with obstetric complications. In conclusion, pregnancy is safe for normotensive mothers with glomerular diseases and normal renal function. Hypertension and impaired renal function at conception seem to carry increased risk for mothers and fetuses. Low-dose immunosuppressive treatment during pregnancy is not harmful for the fetus.

Acute and chronic Chlamydia pneumoniae infection in pregnancy complicated with preeclampsia.

Objective. To investigate whether Chlamydia pneumoniae (Cp) infection is more common in women whose current pregnancy is complicated with preeclampsia (PE) as compared to pregnant women without PE. Methods. Thirty pregnant women with PE and 30 pregnant women without PE were studied between 29 and 30 weeks of gestation. The presence of an acute or chronic Cp infection was determined by the estimations of serum IgG, IgM, and IgA Cp antibodies. Results. None of the women were diagnosed as having acute Cp infection. Prevalence of chronic Cp infection was 53 and 66% in the PE and control groups, respectively (X2, p = 0.068). Conclusion. Chronic Cp infection is not more common in women whose pregnancy is complicated with PE as compared to pregnant women without PE. Therefore, no association between Cp infection and PE can be established.

Mosaic ring X chromosome in a case of secondary amenorrhea

OBJECTIVE To report an unusual case of secondary amenorrhea in a 17-year-old adolescent with normal sexual development who proved to have a karyotype 46,XX/46,X,+ringX/47,XX,+ringX. DESIGN Case report. SETTING Hospital, tertiary level of clinical endocrine care. PATIENT(S) A 17-year-old patient with secondary amenorrhea and normal sexual characteristics with no stigmata of Turner syndrome. INTERVENTION(S) Clinical history, hormonal markers, cytogenetic analysis. MAIN OUTCOME MEASURE(S) Cytogenetic analysis by G-banding technique, multicolor fluorescence in situ hybridization, and multicolor banding analysis on peripheral blood lymphocytes. RESULT(S) The presence of mosaicism in 12% of metaphases indicating a ring X chromosome with one or two normal X chromosomes, forming a karyotype 46,XX/46,X, +ringX/47,XX,+ringX. CONCLUSION(S) Our findings indicate the necessity for cytogenetic studies in certain cases of amenorrhea. This is a very rare karyotype in patients with secondary amenorrhea.

Regulatory Τ-cell differentiation between maternal and cord blood samples in pregnancies with spontaneous vaginal delivery and with elective cesarian section.

Citation Bili H, Fleva A, Pados G, Argyriou T, Tsolakidis D, Pavlitou A, Tarlatzis BC. Regulatory T‐cell differentiation between maternal and cord blood samples in pregnancies with spontaneous vaginal delivery and with elective cesarian section. Am J Reprod Immunol 2011; 65: 173–179

Thyrotropin receptor autoantibodies and early miscarriages in patients with Hashimoto thyroiditis: a case–control study

Abstract We have previously hypothesized that early miscarriage in women with Hashimoto thyroiditis might be the result of a cross-reactivity process, in which blocking autoantibodies against thyrotropin receptor (TSHr-Ab) antagonize hCG action on its receptor on the corpus luteum. To test this hypothesis from the clinical perspective, we investigated the presence of TSHr-Ab in Hashimoto thyroiditis patients with apparently unexplained, first-trimester recurrent miscarriages compared to that in Hashimoto thyroiditis patients with documented normal fertility. A total of 86 subjects (43 cases and 43 age-matched controls) were finally included in a case–control study. No difference in the prevalence of TSHr-Ab positivity was detected between cases and controls (Fisher’s exact test, p value = 1.00). In patients with recurrent miscarriages, TSHr-Ab concentrations did not predict the number of miscarriages (univariate linear regression, p value = 0.08). These results were robust in sensitivity analyses, including only cases with full investigation or those with three or more miscarriages. We conclude that no role could be advocated for TSHr-Ab in the aetiology of recurrent miscarriages in women with Hashimoto thyroiditis.