Tally Levy

Severe abdominal complications after transvaginal ultrasonographically guided retrieval of oocytes for in vitro fertilization and embryo transfer

Severe life-threatening complications as a result of ultrasonically guided ovum pick-up for IVF may rarely occur. We report 14 cases, out of 3,656 patients undergoing the procedure, presenting with a clinical picture of acute abdomen. In 9 patients tubo-ovarian and pelvic abscess were diagnosed; 3 were treated by laparotomy, whereas in the other 6, culdocentesis and drainage were performed. In 3 cases severe intra-abdominal bleeding occurred with 1 requiring laparotomy and hemostasis, whereas in the others laparoscopic drainage and hemostasis were sufficient. Ruptured endometriotic cystic masses caused acute abdomen in 2 patients; partial oophorectomy and drainage were essential operative procedures. We conclude that although severe postovum retrieval complications are rare, one has to be aware of their occurrence with the aim of accurate diagnosis and prompt intervention.

In vitro fertilization and embryo transfer for the treatment of infertility associated with polycystic ovary syndrome

OBJECTIVE To examine the outcome of treatment with IVF-ET of women with polycystic ovarian syndrome (PCOS) who failed to conceive on conventional treatment. DESIGN Retrospective analysis with an age-matched control group. SETTING University hospital infertility clinic and IVF unit. PATIENTS. INTERVENTIONS Sixty-eight women with PCOS who had failed to conceive on treatment with clomiphene citrate and during six ovulatory cycles on gonadotropins underwent 208 cycles of IVF-ET. An age-matched group of 68 women with a tubal mechanical factor who received 143 treatment cycles during the same period served as controls. MAIN OUTCOME MEASURES Cumulative conception rates, the cumulative livebirth rates, and IVF-ET data were compared between the two groups. Results of treatment with and without GnRH agonist (GnRH-a) within the groups were also compared. RESULTS A comparison of PCOS and mechanical factor (control) groups showed almost identical results at 6 months for cumulative conception rate (82% versus 85%) and cumulative livebirth rate (69% versus 65%). Significantly more oocytes were retrieved but a smaller percentage fertilized in PCOS, and the pregnancy rate per ET did not differ between the two groups (23% versus 26%). Treatment with GnRH-a and gonadotropins as opposed to gonadotropins alone improved the cumulative conception rate, miscarriage rate, and cumulative livebirth rate in the PCOS but not in the control group and improved fertilization rates in both groups. CONCLUSIONS For patients with PCOS who fail to conceive with gonadotropin treatment, IVF-ET is a successful treatment alternative, producing results equal to those for women with a mechanical tubal factor. Better results were achieved with GnRH-a in women with PCOS but made no difference to those with a mechanical tubal factor compared with treatment with gonadotropins alone.

Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome

OBJECTIVE To compare the effect of treatment with gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropins (hMG) with that of gonadotropins only, on the cumulative livebirth rate and miscarriage rate of pregnancies achieved in women with polycystic ovarian syndrome (PCOS). DESIGN Retrospective analysis of the outcome of 97 pregnancies according to the treatment protocol, with or without GnRH-a. Calculation of miscarriage rate and cumulative livebirth rate by life-table analysis. SETTING Infertility clinic and in vitro fertilization (IVF) unit. PATIENTS Women with polycystic ovaries (n = 239) who were clomiphene citrate failures and received either GnRH-a/hMG (n = 110) or gonadotropins only (n = 129) for ovulation induction (n = 138) or superovulation for IVF (n = 101). INTERVENTIONS For ovulation induction, hMG was given in a step-up, individually adjusted dose scheme. For IVF, three ampules of pure follicle-stimulating hormone were given for 3 days followed by three ampules per day hMG and then individual dose adjustment. Gonadotropin-releasing hormone agonist (Decapeptyl, D-Trp6, microcapsules, 3.75 mg) was given in a single dose 2 weeks before gonadotropin treatment. MAIN OUTCOME MEASURES The rate of early miscarriages (< 12 weeks) per pregnancies achieved was analyzed, and the cumulative livebirth rate for each treatment group was calculated by life-table analysis. RESULTS Miscarriage rates after treatment in ovulation induction with (16.7%) and without GnRH-a (39.4%) and in IVF with (18.2%) and without GnRH-a (38.5%) were almost identical and were therefore analyzed together. Of pregnancies achieved with GnRH-a, 17.6% miscarried compared with 39.1% of those achieved with gonadotropins alone. Cumulative livebirth rate after four cycles for GnRH-a was 64% compared with 26% for gonadotropins only. CONCLUSIONS Cotreatment with GnRH-a/hMG for anovulatory women with PCOS reduces the miscarriage rate and improves the livebirth rate compared with treatment with gonadotropins alone.

A comparative prospective study of conventional regimen with chronic low-dose administration of follicle-stimulating hormone for anovulation associated with polycystic ovary syndrome

OBJECTIVE To compare efficiency of conventional and chronic low-dose regimens for treatment of anovulation associated with polycystic ovary syndrome (PCOS). DESIGN Fifty participants divided into two equal groups. The first group was treated with urinary human FSH using a conventional stepwise protocol and the second group was treated with a regimen of chronic low-dose and small incremental rises with urinary human FSH or with recombinant human FSH for a maximum of three cycles. SETTING Tertiary referral university hospital fertility unit. PATIENTS Fifty infertile women with clomiphene citrate-resistant anovulation associated with PCOS. MAIN OUTCOME MEASURES Pattern of follicular development, amount of FSH required, serum E2 concentrations, cycle fecundity, cumulative conception, and live birth rates. Multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) rates. RESULTS Compared with the conventional dose protocol, the chronic low-dose regimen yielded slightly improved pregnancy rates (40% versus 24%) while completely avoiding OHSS and multiple pregnancies, which were prevalent (11% and 33%, respectively) with conventional therapy. Monofollicular development was induced in 74% versus 27% of cycles, and the total number of follicles > 16 mm and E2 concentrations were half those observed on conventional therapy. CONCLUSIONS For women with PCOS, a chronic low-dose regimen of FSH eliminated complications of OHSS and multiple pregnancies while maintaining a satisfactory pregnancy rate. This modality, thus, has distinct advantages and could well replace conventional gonadotropin therapy for these patients.

The impact of long-term gonadotropin-releasing hormone analogue treatment on preclinical abortions in patients with severe endometriosis undergoing in vitro fertilization-embryo transfer

OBJECTIVE To examine the relationship between endometriosis and preclinical abortions and to evaluate the effect of gonadotropin-releasing hormone analogue (GnRH-a) therapy on these pregnancies. DESIGN AND PATIENTS Of 67 women with severe endometriosis referred to us for in vitro fertilization-embryo transfer (IVF-ET), 32 underwent ovarian stimulation for oocyte retrieval with menotropins (protocol A), whereas the other 35 were admitted for the procedure after a 6-month period of hormonal suppression with a GnRH agonist (protocol B). The clinical impact of the preclinical and clinical pregnancies in both treatment protocols were evaluated on the basis of oocyte classification and embryo quality score. SETTING All patients were treated in our IVF Unit. MAIN OUTCOME MEASURE Clinical pregnancy was used as our main outcome measure of success. RESULTS A significantly higher number of preclinical pregnancies (P less than 0.0001) occurred in patients treated by protocol A. After GnRH-a treatment, the preclinical pregnancy rate declined significantly (P less than 0.0001), whereas the clinical pregnancy rate per cycle and per transfer rose significantly (P less than 0.0001 and P less than 0.0001, respectively). Furthermore, clinical pregnancies had a significantly better mean embryo quality score in comparison with preclinical pregnancies (P less than 0.0001). CONCLUSIONS It is concluded that combining GnRH-a therapy before IVF-ET provides an improved treatment modality for preclinical abortions and infertility associated with severe endometriosis.

Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences.

BackgroundOvarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer), while existing at a nearly undetectable level in the surrounding normal tissue.MethodsH19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH) using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer.ResultsH19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth.ConclusionThese observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure.

The role of purified follicle stimulating hormone therapy in the male partner before intracytoplasmic sperm injection

OBJECTIVE To evaluate the impact of long-term purified FSH (pFSH) therapy in male partners before intracytoplasmic sperm injection (ICSI). DESIGN Prospective, randomized, controlled study. SETTING Large university-based IVF unit. PATIENT(S) Seventy-eight patients made up the study and control groups (39 patients each). All patients had severe male factor infertility. INTERVENTION(S) Induction of ovulation, oocyte retrieval, ICSI, and ET were carried out in both groups. In the study group, male partners received pFSH (75 IU FSH, <1 IU LH) for > or = 50 days before oocyte retrieval. MAIN OUTCOME MEASURE(S) Fertilization rate, embryo quality, implantation and pregnancy rates. RESULT(S) Fertilization and pregnancy rates were higher in the study group (68% and 35.9%, respectively) were higher than in the control group (59% and 17.9%, respectively), although the differences did not reach statistical significance. The implantation rate was significantly higher in the study group (15.5% versus 6.5%). The study group showed a trend toward a higher number of better-quality embryos per transfer (mean +/- SD, 2.2 +/- 1.6 versus 1.6 +/- 1.6). CONCLUSION(S) Purified FSH therapy in male partners before ICSI improves implantation rate. Improved embryo quality may be a contributory factor.

The residual ovary syndrome: a 20-year experience

OBJECTIVE To address the controversy of ovarian preservation during a hysterectomy for benign indications by using our experience with residual ovary syndrome (ROS). STUDY DESIGN Over a period of 20 years, 2561 hysterectomies (during which one or both ovaries were preserved) were performed at the Golda Medical Center, Israel. A retrospective, quasi, case-control analysis was undertaken. RESULTS The incidence of ROS was 2.85%. While chronic pelvic pain was the principle indication for subsequent reexploration in 52 patients (71.3%), an asymptomatic pelvic mass noted during routine follow-up examination accounted for 24.6% of operations for ROS. The majority (75.4%) of patients underwent surgery during the first 10 years, while the highest incidence occurred within the first 5 years (46.6%). Furthermore, histological examination revealed functional cysts, benign neoplasm and ovarian carcinoma in 50.7%, 42.6% and 12.3% of the cases, respectively (in nine patients more than one pathology was observed). CONCLUSIONS Since ROS was found to occur in 1/35 women who had undergone previous hysterectomies mainly due to physiologic ovarian function and benign cyst formation, but not malignancy, we believe that routine oophorectomy is justified in premenopausal women over 45 years of age. However, the final decision to perform elective oophorectomy at the time of hysterectomy for benign disease should be established on an individual basis, taking into consideration age, individual and family risk factors, the patients preference and ability to ensure long-term compliance to exogenous hormone replacement therapy.

Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement

AIMS To assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy. METHODS Multicenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed. RESULTS Five hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients). CONCLUSION Using a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.

Combined weekly carboplatin and paclitaxel as primary treatment of advanced epithelial ovarian carcinoma

OBJECTIVE To evaluate safety and outcome of weekly carboplatin and paclitaxel as the initial postoperative adjuvant chemotherapy for epithelial ovarian carcinoma (EOC) patients. METHODS Patients with stage IC-IV epithelial ovarian cancer (EOC) primary peritoneal or tubal carcinoma were enrolled in this phase II study. Intravenous carboplatin (area under the curve 2) and paclitaxel (80 mg/m(2)) were administered on days 1, 8, and 15 of a 28-day cycle for 6-8 cycles. Cytoreductive surgery was performed as primary treatment or after 3 cycles of weekly neoadjuvant chemotherapy, followed postoperatively by an additional 3 cycles of chemotherapy. RESULTS Sixty-four women (median age 65 years, range 39.9-82.8) were enrolled. Fifty-six of them (87.6%) were diagnosed with stage III-IV disease. Neutropenia was the most common hematological toxicity: 25% of the subjects had grade 3-4 neutropenia, 34.4% were supported by GCSF and 15.6% received epoetin. The majority (89%) of the patients had grade 1 and only 7.8% had grade 2 alopecia. 7.8% had grade 3 fatigue and 14.1% had grade 2 and 3.1% grade 3 neuropathy, none developed grade 4 neuropathy and only 6.3% had some residual neuropathy at >6 months after treatment. With a median follow-up of 31.5 months (range 5.9-57.3), estimated median survival was 52.0 months and median progression-free survival 25.74 (8.4-57.3) months (95% CI, 21.2-30.3). Overall and complete response rates were 92.1% and 64.1% respectively. CONCLUSION Weekly carboplatin and paclitaxel as the initial chemotherapy for EOC is a feasible and well tolerated regimen and should be further evaluated in a larger phase III study.