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Biomedical subjects

D Meirow

Publications and source records attributed to D Meirow.

At least 19 recordsLinked to original sources
PubMed2001

Administration of cyclophosphamide at different stages of follicular maturation in mice: effects on reproductive performance and fetal malformations.

This study assessed reproductive performance, fetal viability and teratogenicity in female mice exposed to cyclophosphamide across a timeline corresponding to different stages of follicle maturation. Pregnancies were established in female Balb/c mice 1-4 weeks after administration of a non-sterilizing dose of cyclophosphamide (75 mg/kg). Each mating group represented a different stage of follicular growth at the time of cyclophosphamide exposure. The number of corpora lutea, pregnancies and fetal resorptions were determined. Surviving fetuses were evaluated for gross malformations. Results indicated that conceptions attributable to follicles exposed to cyclophosphamide at a mature stage had a significantly lower number of implantation sites, 4.82 +/- 1.01 versus 8.27 +/- 0.81 in controls (P = 0.001) and a high resorption rate, 56% +/- 0.11 versus 34% +/- 0.07 in controls (P = 0.05). The proportion of corpora lutea in this group which resulted in viable fetuses was extremely low, 0.2 +/- 0.06 versus 0.51 +/- 0.07 in controls (P = 0.001). Malformation rate was more than 10 times higher in all treated groups (P < 0.05) and a particularly high incidence of 33% (P = 0.0014) was observed in conceptions attributable to oocytes exposed to cyclophosphamide at the earliest stages of follicle growth. With an extended interval between exposure and mating the malformation rate gradually decreased towards normal values in the 12th week group. This study suggests that the effect of cyclophosphamide on female gametes and subsequently on future reproduction is influenced by the stage of oocyte maturation at the time of exposure. Early fertilization post-chemotherapy can result in a high rate of pregnancy failure and high malformation rate. This should be taken into account when considering the use of oocyte retrieval, IVF and embryo cryopreservation in patients currently undergoing chemotherapy.

Abnormalities, Multiple↗
PubMed2000

Reproduction post-chemotherapy in young cancer patients.

High-dose chemotherapy and radiotherapy has increased long-term survival of young patients with cancer. Sometimes however, the price paid is ovarian failure and sterility. It is highly important to detect who are the patients at risk in order to verify when fertility preservation is indicated. With conventional chemotherapy, there is significant differences in ovarian failure rate according to patients age, disease for which patients are treated for, and the drugs used. Bone marrow transplantation in cancer patients almost invariably induced ovarian failure, irrespective of patient age, treatment protocol or administration of hormonal treatment. Moreover, normal reproductive parameters post-chemotherapy does not necessarily imply that the ovaries escaped damage; ovarian injury is not an all or none phenomenon--partial loss of primordial follicle reserve can result in premature menopause as a delayed reaction to treatment. This should be taken into account while consulting former cancer patients about future planed pregnancies. The direct mechanisms of chemotherapy induced ovarian failure are poorly understood. An in vitro study has demonstrated that in the human ovary chemotherapy acts primarily on primordial follicles through induction of apoptotic changes in pregranulosa cells which lead to follicle loss. Protecting fertility potential in females exposed to chemotherapy with IVF and embryo cryopreservation or cryopreservation of ovarian tissue is practiced. Ovarian tissue cryopreservation: A recent study has demonstrated that laparoscopic ovarian biopsy performed with the round biopter is a safe and efficient method for collecting ovarian tissue for cryopreservation in cancer patients. In order to avoid possible hazards of transferring malignant cells, genetic and immunohistochemical markers for detection of minimal residual cancer cells in ovarian tissue are currently used. However, the reproductive potential of this method is still questionable. IVF: IVF and embryocryopreservation is currently used in infertile patients, however, several obstacles prevent it's wide implementation in cancer patients such as the need for male partner and the time needed for ovarian stimulation. A highly important issue is the possible risk of performing IVF and embryo cryopreservation to preserve fertility in females already exposed to chemotherapy. An animal study has raised serious concerns regarding the consequences of chemotherapy on future pregnancies. High abortion and malformation rates related to the different stages of oocyte maturation at the time of exposure to chemotherapy were demonstrated. These results should be taken into account when considering the use of IVF and embryo cryopreservation following chemotherapy treatment in cancer patients.

Adolescent↗
PubMed1999

A laparoscopic technique for obtaining ovarian cortical biopsy specimens for fertility conservation in patients with cancer.

OBJECTIVE: To evaluate the efficacy of a newly designed round biopter as a practical and safe method for collecting ovarian tissue for cryopreservation in young women with cancer before chemotherapy. DESIGN: Prospective study of young women volunteering for research (Leeds, United Kingdom) and patients with cancer (Jerusalem, Israel and Leeds, United Kingdom) undergoing laparoscopic ovarian cortical tissue biopsy and cryopreservation before administration of high-dose radiochemotherapy. SETTING: Two university-based tertiary referral centers of oncology and gynecology (Hadassah Medical Center, Israel; Leeds General Infirmary, United Kingdom). PATIENT(S): Twenty female volunteers undergoing routine laparoscopic gynecologic procedures (age, 25-34 years) and 20 young women (age, 11-30 years) with advanced cancer requiring potentially sterilizing radiochemotherapy. INTERVENTION(S): Cortical ovarian tissue biopsies performed under laparoscopy with use of the round biopter. RESULT(S): The laparoscopic sampling procedure was uncomplicated in all cases. In treated patients, five to six samples were obtained (5 mm in diameter; 2-3 mm in depth) using the round biopter, and radiochemotherapy was administered without delay. In volunteers, no adhesions were noted at repeat laparoscopy (9 patients). All biopsy specimens were cryopreserved, and histologic examination confirmed the presence of many primordial follicles. CONCLUSION(S): Laparoscopic ovarian biopsy performed with the round biopter is a safe and efficient method for collecting ovarian tissue for cryopreservation in patients with cancer.

Adolescent↗
PubMed1999

Vaginal outflow tract obstruction by graft-versus-host reaction.

We describe a 25-year-old patient suffering from vaginal outflow obstruction which presented as secondary amenorrhea during hormone replacement therapy. The patient had undergone bone marrow transplantation for acute myelocytic leukemia, which caused ovarian failure. Oral mucositis associated with a chronic GVH reaction also occurred. For 3 years she was treated with HRT and had regular menses which gradually ceased and were associated with dyspareunia and abdominal cramps. Abdominal US examination demonstrated hematocolpus. Sonography guided adhesiolysis of a dense vaginal obstruction allowed free drainage with histologic confirmation of a graft-versus-host reaction. The possibility of vaginal stricture or obstruction should be considered in all patients after BMT who suffer from graft-versus-host disease.

Adult↗
PubMed1999

Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigative tool.

Studies have shown that ovarian failure is a common side-effect of chemotherapy treatment; however, continuation of regular menses post-treatment does not necessarily imply that the ovaries have escaped damage. This animal study measures directly the primordial follicle (PMF) loss following exposure to chemotherapy and evaluates reproductive outcome following significant destruction of the PMF population. Inbred Balb/c mice aged 5-6 weeks were administered different doses of an alkylating agent, cyclophosphamide, and the total number of PMF remaining in both ovaries was counted. Results show that cyclophosphamide causes PMF destruction in proportion to increasing dose (P = 0.0001). Reproductive performance was assessed after exposure to 75 mg/kg cyclophosphamide, a dose which destroys approximately 50% of PMF reserve, by evaluation of ovulation, mating and pregnancy rates. Reproductive potential of treated mice was not affected compared with controls despite the significant loss of PMF. Our results indicate that reproductive performance is not an accurate parameter for assessing ovarian injury. Rather, histological counting of PMF number more directly reflects the damage caused by chemotherapy to the ovary. This method can be used as a sensitive, inexpensive tool to gauge the damage to fertility caused by new chemotherapy agents or protocols.

Animals↗
PubMed1999

Ovarian injury and modern options to preserve fertility in female cancer patients treated with high dose radio-chemotherapy for hemato-oncological neoplasias and other cancers.

High dose chemotherapy and radiotherapy have radically increased long term survival of young cancer patients. Among the side effects of chemotherapy treatments are ovarian failure and infertility, which are of particularly great concern to young cancer patients. Recently, cryopreservation procedures such as in vitro fertilization and embryo storage, or ovarian tissue cryopreservation have been used to preserve fertility in patients subjected to cancer treatments. Knowledge of the risks and probabilities of ovarian failure as well as the risks of the cryopreservation procedures is crucial for patients and physicians in order to make informed choices that will best serve the patients interests. This article presents data of a prospective study that determines the risk of ovarian failure following exposure to chemotherapy as well as a review of related publications. Progressive, dose-related depletion of primordial follicles is noted on histology, explaining the risk of undergoing premature ovarian failure years after exposure to chemotherapy. The safety of ovarian tissue cryopreservation procedures with a new round biopter was evaluated, as well as the risk of malignant cell transmission. It has been shown that laproscopic ovarian biopsy performed with the round biopter is a safe and efficient method for collection of ovarian tissue in cancer patients. In Hodgkin's disease patients' ovarian cortical tissue obtained for cryopreservation does not contain malignant cells. However the risk of cryopreserving and transferring malignant cells should be tested separately for each disease according to the risk of ovarian metastasis and the ability to detect single malignant cells.

Age Factors↗
PubMed1998

Parasitic ovarian dermoid tumor of the omentum-A review of the literature and report of two new cases.

Two cases of a parasitic omental teratoma which originated from an ovarian dermoid that underwent torsion, autoamputation and omental reimplantation are presented. A review of the literature revealed 23 additional cases of omental teratoma which occurred mostly in females. In some cases, the mature teratoma of the omentum showed histological evidence of ovarian stroma, and was associated with a dermoid tumor of the remaining contralateral ovary. It is generally believed that autoamputation and reimplantation of an ovarian dermoid cyst is the most common etiology of omental teratomas. Abdominal pain is the main presenting symptom of these tumors, and on physical examination a mobile abdominal or pelvic mass is often found. Both ultrasonography with colour flow Doppler and CT-scan are helpful in the diagnosis of dermoid tumors, but the correct diagnosis of omental localisation is extremely difficult. Mature omental teratomas may be treated by simple resection. The immature teratomas of the greater omentum, however, are potentially malignant tumors requiring postoperative chemotherapy and radiotherapy.

Abdominal Pain↗
PubMed1997

Polycystic ovary syndrome. An autoimmune disease?

OBJECTIVE: To determine whether there is an autoimmune cause of polycystic ovary disease (PCOD) implicating antiovarian antibodies in the pathophysiology of the syndrome. STUDY DESIGN: This study examined 31 women diagnosed as having PCOD according to internationally recognized criteria and who attended our infertility clinic during 1994-1995. RESULTS: We could not confirm the findings of previous studies. Only one patient in our group with type II diabetes mellitus had antiovarian antibodies present in her serum. CONCLUSION: It seems that an autoimmune mechanism probably is not of prime importance in this multifaceted syndrome.

Adult↗
PubMed1996

Ovarian hyperstimulation syndrome with low oestradiol in non-classical 17 alpha-hydroxylase, 17,20-lyase deficiency: what is the role of oestrogens?

Ovarian stimulation in a patient who suffered from partial (non-classical) 17 alpha-hydroxylase 17,20 lyase deficiency of the adrenal cortex and gonads is described. Diagnosis was based on measurements of high concentrations of steroid metabolites proximal to the enzymatic block (progesterone, 17-hydropregnenolone and 17-hydroprogesterone); with further rise following adrenocorticotrophic hormone (A-CTH) stimulation, and low steroid concentrations distal to the block. Her basal plasma oestradiol values were low and did not rise even during repeated treatment cycles with maximal ovarian stimulation. However, clinical presentation of ovarian hyperstimulation syndrome (OHSS) developed despite very low oestradiol concentrations, thus seriously questioning the role of oestradiol in the pathogenesis of this condition. The poor correlation between clinical presentation of OHSS and plasma oestradiol values, as presented in this case, supports other data which conclude that oestradiol measurements alone are not sufficient to alert the physician to the possible development of OHSS.

Adrenal Hyperplasia, Congenital↗
PubMed1996

Delivery following intracytoplasmic injection of mature sperm cells recovered by testicular fine needle aspiration in a case of hypergonadotropic azoospermia due to maturation arrest.

This is the first reported delivery following intracytoplasmic sperm injection (ICSI) of mature live testicular sperm cells collected in a case of hypergonadotrophic azoospermia with maturation arrest. The 30 year old couple presented with primary infertility of 11 years duration, the man being submitted in childhood to five orchidopexy operations for the treatment of cryptorchism. He had elevated serum follicle stimulating hormone (FSH; 18.8 IU/I), an atrophic left testis and a normal sized right testis, the biopsy of which diagnosed maturation arrest and focal scarring. The couple refused donor insemination for religious reasons and the only option was an attempt at testicular sperm collection. Multiple testicular and epididymal fine needle aspirations were performed, using an aspiration handle loaded with 20 ml syringe and 21-23 gauge butterfly needles. The mature spermatozoa recovered were used to inseminate the oocytes by ICSI. Prior to this procedure, the patient's wife underwent ovulation induction using a long protocol of mid-luteal gonadotrophin-releasing hormone analogue/human menopausal gonadotrophin (GnRHa/HMG). At oocyte retrieval, ten oocytes were recovered. Eight live sperm cells were recovered from the aspirates of the right testis. Following ICSI into four metaphase II and two metaphase I oocytes, one mature oocyte was fertilized, cleaved and was transferred to the uterus 48 h after oocyte retrieval. The patient conceived and delivered a 3300 g boy at term. In conclusion, our results demonstrate that this novel approach should be considered in cases with hypergonadotrophic azoospermia due to testicular failure. Further experience is needed to establish the exact criteria for its use.

Adult↗
PubMed1996

Dyslipidaemia in polycystic ovarian syndrome: different groups, different aetiologies?

The objective was to study the pathophysiology of the dyslipidaemia in polycystic ovarian syndrome (PCOS) patients, and to determine how it is related to hyperinsulinaemia, hyperandrogenism and dehydroepiandrosterone sulphate (DHEA-S) concentrations. The lipoprotein lipid profile, anthropometric measurements, endocrine profile and the presence of insulin resistance were evaluated in 31 PCOS patients and 20 age-matched healthy women, who served as controls. PCOS patients had higher fasting insulin concentrations, higher body mass indexes (BMI) and were hyperlipidaemic, with higher total cholesterol, low density lipoprotein (LDL) and triglyceride (TG) concentrations. There were no relationships between plasma lipids and anthropometric variables in the patient group as a whole. Insulin-resistant (IR) and non-IR (NIR) PCOS patients were then evaluated separately. Obesity with marked hyperandrogenism were the predominant features in patients with IR. NIR patients were not obese and had significantly less hyperandrogenism. The adrenal androgen DHEA-S was at the upper limit of its normal range in both groups. However, both PCOS subgroups exhibited similar significant abnormalities in terms of their lipid parameters. Insulin and DHEA-S concentrations were positively correlated with total cholesterol, LDL and TG, and negatively correlated with high density lipoprotein, in IR patients. In NIR subjects, insulin was not correlated with any of the lipids and DHEA-S was negatively related to cholesterol and LDL. Anthropometric variables were related to lipids in only the NIR patients. Thus PCOS subjects as a group exhibit dyslipidaemia, characterized by increased total cholesterol, LDL and TG concentrations. When divided into IR and NIR subjects, there were no differences in the degree of lipid abnormalities, despite significant variations in the BMI and androgen status. Thus, in PCOS subjects, dyslipidaemia may occur irrespective of insulin resistance. Insulin and DHEA-S concentrations were positively correlated with an atherogenic lipid profile in the IR group only. As distinct from syndrome X when IR was present, dyslipidaemia was not related to body weight or the waist:hip ratio. In the NIR group there was no relationship between lipids and insulin; DHEA-S, on the other hand, was negatively related to cholesterol and LDL concentrations. Thus, dyslipidaemia in PCOS patients may occur irrespective of insulin resistance, and may have different metabolic aetiologies depending on DHEA-S metabolism. It remains to be seen whether the two types of PCOS are associated with different risks for ischaemic heart disease.

Adult↗
PubMed1995

Appraisal of gamete intrafallopian transfer.

OBJECTIVE: To collect results of gamete intrafallopian transfer on a large scale in order to compare treatment indications, results, and factors which influence the success rates; to evaluate whether gamete intrafallopian transfer is well-established and what the real place of this procedure is among other assisted reproduction techniques. DESIGN: Data relating to gamete intrafallopian transfer were collected from World Reports, national registries of different countries and meta-analysis of medical publications during the years 1986-1991. SUBJECT: Official registries reported 47,200 treatment cycles and 18,759 treatment cycles were analysed from ten medical publications. RESULTS: The procedure accounts for 13.5% of all assisted reproduction techniques but its popularity varies significantly among countries. The same indications for gamete intrafallopian transfer are followed by all countries, but great differences exist with regard to the proportional share of each etiology. Also, the share has changed considerably over the years. TREATMENT OUTCOME: 10,667 clinical pregnancies were reported which represent 24% of treatment cycles and 29% of ovum pick-up. The live birth rate was 23.3%; abortion rate, 22%; and ectopic pregnancy rate, 5.5%. The stillbirth rate was 2.3% and the malformation rate was 2.8%, not confined to specific organs or systems. There were 19.5% twins, 4.6% triplets and 0.3% quadruplets or more. The number of transferred oocytes influenced pregnancy rates: 28% for transfer of four oocytes and only 10% following transfer of one oocyte. The cause of infertility might influence the results and the poorest results are obtained for male factor infertility. In most cases correlation of success rates reported by leading units through medical publications closely resembles the overall national registries results. Indications for this treatment were broadened over the years, but its role among other assisted reproduction technologies is not agreed upon, especially for male factor and unexplained infertility. CONCLUSIONS: Gamete intrafallopian transfer carries an overall higher pregnancy rate than in vitro fertilization. Quality control by professional or public associations should be established and more research employed over indications for treatment and results in order to establish when GIFT is the treatment of choice and when other modes of treatment should be preferred.

Australia↗
PubMed1995

Effects of low-dose estrogen oral contraceptives on weight, body composition, and fat distribution in young women.

OBJECTIVE: To determine prospectively whether the use of low-dose estrogen oral contraceptives (OC) is associated with changes in weight, body composition, or fat distribution. DESIGN: Anthropometric measurements were performed in 49 healthy young (16 to 21 years old) women before commencement of OC use (30 micrograms ethinyl estradiol [EF2] plus 75 micrograms gestodene) and after three and six treatment cycles. Thirty one age- and weight-matched women who were not using OC served as controls. SETTING: Outpatient gynecological clinic of Hadassah Medical Center, a tertiary level hospital, and the "Shilo" voluntary service for the prevention of unwanted pregnancy. MAIN OUTCOME MEASURES: Anthropometric measurements included body mass index (BMI), waist-to-hip girth ratio, and body composition (the percentage of body fat and water), estimated by mean of infrared interactance. RESULTS: In the group of OC users, baseline BMI, percent fat, percent water, and waist-to-hip girth ratio were 21.1 +/- 0.32 (kg/m2), 23.8% +/- 0.63%, 57.4% +/- 0.39%, and 0.73 +/- 0.01, respectively, and did not change significantly after six cycles (20.6 +/- 0.41 [kg/m2], 23.9% +/- 0.57%, 58.1% +/- 0.49%, and 0.72 +/- 0.03, respectively). These measurements were not significantly different when compared with the nonusers. Fifteen OC users (30.6%) gained weight (> 0.5 kg). Weight gain was due to a significant accumulation of fat (from 22.5% +/- 1.1% to 25.6% +/- 0.74%), whereas the percentage of body water remained stable. The waist-to-hip girth ratio also was not changed significantly. Similarly, 11 nonusers (35.4%) gained weight because of similar nonabdominal fat accumulation. Ten OC users (20.4%) lost weight (57 kg +/- 1.51 to 55.4 +/- 1.47 [mean +/- SEM]) and 6 nonusers (19.3%) also lost weight (59 kg +/- 1.42 to 57.3 +/- 1.92). In both groups the loss of weight was not associated with significant change in body composition. CONCLUSIONS: The use of low-dose OC (EE2 plus gestodene) was not associated with overall impact on weight, body composition, or fat distribution. However, when weight gain did occur during OC use, it was due to increase in body fat and not in volume of body water, and it was not associated with changes in fat distribution.

Adipose Tissue↗
PubMed1995

Insulin resistant and non-resistant polycystic ovary syndrome represent two clinical and endocrinological subgroups.

We studied the clinical and endocrine features of 35 patients with polycystic ovary syndrome (PCOS) who are either insulin resistant or non-insulin resistant. The occurrence of insulin resistance was determined by measuring insulin and glucose concentrations following a standard 75 g oral glucose load. All patients were evaluated by anthropometric measurements: body mass index (BMI), percentage of body fat (BCF) and waist-to-hip ratio (W/H), degree of hirsutism (Ferriman-Gallwey method) and endocrine profile. Fourteen patients had insulin resistance of unknown origin whereas four were due to a type A insulin receptor mutation, and 17 were non-insulin resistant. The insulin resistant patients were significantly more obese (higher BMI P < 0.0001, BCF P < 0.002 and W/H ratio P < 0.005) and were more hirsute (P < 0.002) than the non-insulin resistant patients. Testosterone concentrations were significantly higher in the insulin resistant group than in the non-insulin resistant group (2.65 versus 1.37 nmol/l; P < 0.027), whereas sex hormone-binding globulin was lower in insulin resistant patients (30.61 versus 19.48 nmol/l; P < 0.02). Non-insulin resistant patients showed a high luteinizing hormone to follicle stimulating hormone ratio, while a normal ratio was found in the insulin resistant subpopulation (2.94 versus 1.34; P < 0.0001). We concluded that PCOS comprises two subpopulations, one with insulin resistance of different aetiologies and the other which has no insulin resistance. These two groups differ in their anthropometric and endocrine features. The diagnosis of insulin resistance in PCOS can be easily determined by the insulin response to an oral glucose tolerance test.

Adult↗