A. Raziel

Intracytoplasmic injection of fresh and cryopreserved testicular spermatozoa in patients with nonobstructive azoospermia—a comparative study

OBJECTIVE To compare the outcome of intracytoplasmic sperm injection (ICSI) with fresh and frozen-thawed testicular spermatozoa in patients with nonobstructive azoospermia. DESIGN Retrospective analysis of consecutive ICSI cycles. SETTING In Vitro Fertilization Unit, Assaf Harofeh Medical Center. PATIENT(S) Eighteen with nonobstructive azoospermia in whom testicular sperm was found after testicular sperm extraction. INTERVENTION(S) Testicular sperm retrieval, cryopreservation, and ICSI with fresh or frozen-thawed testicular spermatozoa. MAIN OUTCOME MEASURE(S) Two-pronuclear fertilization; embryo cleavage rates, mean number of embryos transferred per cycle, and their relative quality, embryo implantation, clinical pregnancy, and ongoing pregnancy rates (PRs) per ET. RESULT(S) No statistically significant differences were noted in all parameters examined between ICSI cycles with fresh or cryopreserved testicular spermatozoa from the same nine patients and comparing all ICSI cycles performed; with fresh (25 cycles) and thawed (14 cycles) testicular spermatozoa, respectively: two-pronuclear fertilization, 47% versus 44%; embryo cleavage rates, 94% versus 89%; implantation rates, 9% versus 11%; and clinical PR, 26% versus 27%. The delivery or ongoing PR using fresh sperm was better (21% versus 9%), but the difference did not reach statistical significance. The cumulative clinical PRs and ongoing PRs per testicular sperm extraction procedure were 36% and 24%, respectively. CONCLUSION(S) Testicular sperm cryopreservation using a simple freezing protocol is promising in patients with nonobstructive azoospermia augmenting the overall success achieved after surgical sperm retrieval.

Meiotic Arrest In Vitro by Phosphodiesterase 3-Inhibitor Enhances Maturation Capacity of Human Oocytes and Allows Subsequent Embryonic Development

Abstract Controlling nuclear maturation during oocyte culture might improve nuclear-cytoplasmic maturation synchrony. We aimed to evaluate the quality of in vitro-matured, germinal vesicle (GV)-stage human oocytes following a prematuration culture (PMC) with a meiotic arrester, phosphodiesterase 3-inhibitor (PDE3-I). Follicles (diameter, 6–12 mm) were retrieved 34–36 h post-hCG administration from informed, consenting patients who had undergone controlled ovarian stimulation. Cumulus-enclosed oocytes (CEOs) presenting moderate expansion or full compaction were placed in PMC with the PDE3-I, Org9935, for 24 or 48 h. Subsequently, oocytes were removed from PMC, denuded of cumulus cells, matured in vitro, and fertilized, and the resulting embryos were cultured. In the presence of PDE3-I, approximately 98% of the oocytes were arrested at the GV stage. Following PDE3-I removal, oocytes acquired a higher maturation rate than oocytes that were immediately denuded of cumulus cells after retrieval and in vitro matured (67% vs. 46%, P = 0.01). In controls, immature CEOs retrieved with moderate expansion reached higher maturation rates compared to fully compacted CEOs, but in PMC groups, high values of maturation were achieved for both morphological classes of CEOs. No effect of PMC on fertilization was observed. A 24-h PMC period proved to be the most effective in preserving embryonic integrity. Similar proportions of nuclear abnormalities were observed in embryos of all in vitro groups. In summary, PMC with the specific PDE3-I had a beneficial effect on human CEOs by enhancing maturation, benefiting mainly the fully compacted CEOs. This resulted in an increased yield of mature oocytes available for insemination without compromising embryonic development. These results suggest that applying an inhibitor to control the rate of nuclear maturity by regulating intraoocyte PDE3 activity may allow the synchronization of nuclear and ooplasmic maturation.

Hypercoagulable Thrombophilic Defects and Hyperhomocysteinemia in Patients with Recurrent Pregnancy Loss

PROBLEM: Placental perfusion may be compromised by increased thrombosis that leads to pregnancy complications and recurrent pregnancy loss (RPL). Since heritable thrombophilic defects and hyperhomocysteinemia are associated with increased thrombosis, their prevalence was evaluated in RPL patients with special emphasis on combinations of the above pathologies.
 METHODS OF STUDY: Evaluation of the prevalence of heritable thrombophilic defects (protein S, protein C, anti‐thrombin III deficiency, and the mutations for factor V Leiden, methylenetetrahydrofolate reductase [MTHFR], and prothrombin gene), hyperhomocysteinemia, and combinations of these pathologies in 36 non‐pregnant recurrent aborters compared with 40 parous women.
 RESULTS: We found a relatively high prevalence of deficiencies of plasma coagulation proteins in RPL patients compared with the controls. A non‐significant different increase in factor V Leiden mutation was detected (6/36 [16%] compared with 2/40 [5%] in the control group, P=0.14]. Hyperhomocysteinemia was found in 31% of the RPL patients. MTHFR mutation homozygosity was found in 6/36 (16%) of the aborting patients. Combinations of hyperhomocysteinemia and MTHFR mutation were found in three patients, with folate deficiency in two patients, and with B12 deficiency in three.
 CONCLUSIONS: Combinations of gene mutations, plasma protein deficiencies, and hyperhomocysteinemia, which are associated with an increased thrombotic risk, are more common in RPL patients compared with controls. Large‐scale prevalence studies are needed in order to draw conclusions as to the causative relation of such a condition and RPL.

Investigation of the uterine cavity in recurrent aborters

To prospectively compare the diagnostic ability of both HSG and diagnostic hysteroscopy in recurrent aborters, an HSG followed by a diagnostic hysteroscopy was performed in 106 patients during an investigation into recurrent abortions. The uterine cavity findings on HSG and at hysteroscopy were compared. Among the 60 abnormal HSG patients, intrauterine pathology was demonstrated in 37 (34.9%). Among the 46 normal HSG patients, a normal uterine cavity was found in 33 (31.3%). The sensitivity of the HSG in revealing intrauterine abnormalities was therefore 79% and its specificity 60%. In 23 pathologic HSG, no abnormalities were seen by hysteroscopy. In 13 cases, hysteroscopy demonstrated mild intrauterine findings overlooked by HSG. The false-positive rate was 38% and the false-negative rate was 28%. Hysterosalpingography showed a high false-positive rate, especially in the intrauterine adhesions group. In view of the low specificity and high false-positive and false-negative rates, we believe that hysteroscopic evaluation of the uterine cavity is superior to HSG in recurrent abortions.

Ovarian pregnancy: A report of twenty cases in one institution

A series of 20 cases of primary ovarian pregnancy that were diagnosed and treated in one institution is reported. The prevalence rate of 1:3600 deliveries seems to be increasing in past years and comprises 3.3% of all extrauterine pregnancies. Clinical presentation, possible pathogenesis, diagnostic steps, preferred management, and future fertility are detailed. Inasmuch as all our 18 fertile patients used an intrauterine contraceptive device before the operation, special emphasis is made on the controversial relationship between use of intrauterine contraceptive devices and ovarian pregnancy.

Very Low Sperm Count Affects the Result of Intracytoplasmic Sperm Injection

AbstractPurpose: The aim was to examine the influence of extremelylow sperm count on intracytoplasmic sperm injection(ICSI) outcome. Methods: Over 1000 consecutive unselected ICSI cycleswere divided into four groups according to spermconcentration of their patients: A, cryptozoospermia, 107 patients; B,sperm concentration of ≤ 1×104, 146 patients; C, spermcount of 1×104–1×105, 135 patients; and concentration of≤ 1×105 and < 10×106/ml (control group), 688 patients. Results: A significant decrease in pregnancy rate wasnoticed in the cryptozoospermic group in comparison to thecontrol group (20% vs. 31%). Fertilization rate in group Awas significantly lower in comparison to all other groups,respectively (46% vs. 52%, 54%, 61%). Embryo quality wasinferior in group A in comparison to the control group. Ahigher yet not statistically significant abortion rate wasobserved in the cryptozoospermic group (as well as in groupC) (30%, 27%) compared to the control group (15%). Conclusions: It seems that an extremely low sperm counthas a negative effect on the outcome of ICSI. Neverthelesspatients with cryptozoospermia should not be offered ICSItreatment with the ejaculated sperm before karyotype isestablished.

Intracytoplasmic sperm injection outcome of ejaculated versus extracted testicular spermatozoa in cryptozoospermic men

OBJECTIVE To compare intracytoplasmic sperm injection (ICSI) outcome of patients with cryptozoospermia after use of ejaculated versus testicular sperm in different cycles of the same patients. DESIGN Retrospective cohort study. SETTING University-affiliated infertility center. PATIENT(S) A total of 17 patients with cryptozoospermia who underwent a total of 116 ICSI cycles. INTERVENTION(S) The patients initially underwent several ICSI cycles using ejaculated sperm (n = 68, 58.6%) that were followed by ICSI cycles using testicular sperm (n = 48, 41.4%). MAIN OUTCOME MEASURE(S) Fertilization rate, pregnancy rate (PR). RESULT(S) There were no significant differences in fertilization rates between the two subgroups. A comparison between testicular sperm extraction (TESE) versus ejaculated sperm cycles revealed significantly higher implantation rate (20.7% vs. 5.7%), higher PR (42.5% vs. 15.1%), and higher take home baby rate (27.5% vs. 9.4%). A multivariable logistic regression analysis showed three significant predictors for pregnancy, namely the use of testicular sperm (odds ratio [OR] 5.1, 95% confidence interval [95% CI] 1.8-14.8), use of motile sperm (OR 12.9, 95% CI 2.1-79.1), and female age (OR 0.83, 95% CI 0.7-0.9). CONCLUSION(S) Testicular sperm extraction is justified in patients with cryptozoospermia who fail to conceive by ICSI using ejaculated spermatozoa, as it offers higher PR.

Increased frequency of female partner chromosomal abnormalities in patients with high-order implantation failure after in vitro fertilization

OBJECTIVE To find the type and frequency of chromosomal abnormalities in a selected group of high-order implantation failure (> or =6 IVF trials and > or =15 transferred embryos) and to evaluate its impact on pregnancy outcome. DESIGN A retrospective study. SETTING In vitro fertilization (IVF) unit in a university affiliated hospital. PATIENT(S) Sixty-five couples with high-order implantation failure in IVF and embryo transfer. INTERVENTION(S) In vitro fertilization/embryo transfer (ET), work-up for implantation failure, cytogenetic analysis of the couple. MAIN OUTCOME MEASURE(S) We studied the type and frequency of chromosomal changes, quality of embryos, cumulative pregnancy rates, and pregnancy outcome. RESULT(S) The mean number of treatment cycles per patient, before karyotyping was 7.8 +/- 2.4 (range: 6 to 16 cycles). The mean cumulative number of all transferred embryos per patient was 25.7 +/- 10.3 (range: 9 to 65 embryos). Chromosomal abnormalities were found in 10 of 65 (15.4%) cases: translocations in six, mosaicism in two, and inversion or deletion in another two. The morphologic characteristics of the transferred embryos and the cumulative pregnancy rates were similar in patients with implantation failure with and without chromosomal changes. Three of the 16 patients with abnormal karyotype delivered and three miscarried within a follow-up period of 1 year. CONCLUSION(S) A high frequency of chromosomal aberrations was found in a selected group of high-order implantation failures, a similar frequency to recurrent miscarriages. Karyotyping is recommended as part of the work-up for repeated implantation failure in assisted reproduction. Treatment options include further IVF trials, preimplantation genetic diagnosis, or oocyte donation, tailored according to the type of chromosomal change. An international registry should be considered to assist in counseling these patients.

Hysteroscopic findings after missed abortion

OBJECTIVE To identify the relation of missed abortions and intrauterine pathology. DESIGN A postabortal hysteroscopy was performed 8 to 12 weeks after a dilatation and curettage (D&C) for missed abortion. SETTING Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin, Israel. PATIENTS Sixty patients after a D&C for a missed abortion. MAIN OUTCOME MEASURES The hysteroscopic appearance of the uterine cavity. RESULTS Intrauterine adhesions occurred in only 10 patients (16.7%) with most of them of the mild type. A previous missed abortion was recorded in 60% of these cases. Uterine anomaly was found in one quarter of the cases, mainly an incomplete uterine septum. CONCLUSION We believe that missed abortion does not predispose for intrauterine adhesions to the extent that was previously believed. A partial uterine septum is a major factor predisposing for the occurrence of missed abortion. Hysteroscopy after a missed abortion is an easy and efficient means for both identifying such uterine anomaly and excluding intrauterine adhesions.

The influence of thyroid function on serum lipid profile.

Serum triglycerides, cholesterol, HDL-C and LDL-C levels as well as the LDL/HDL cholesterol ratio were determined in 11 patients suffering from hyperthyroidism and 7 patients suffering from hypothyroidism, and compared with those of 19 sex-and age-matched controls. In hypothyroidism a net increase of all lipid values was observed. In hyperthyroidism cholesterol and LDL-C values were reduced while those of the triglycerides and HDL-C were unchanged as compared with controls. The LDL/HDL cholesterol ratio in either group of patients was lower than in controls, the lowest being observed in thyrotoxicosis.