IVF outcome with cryopreserved testicular sperm.

The introduction of intracytoplasmic sperm injection and the use of spermatozoa extracted from the testicles have changed the option for conception for azoospermic patients. The purpose of the present study was to evaluate the IVF outcome after using cryopreserved testicular sperm samples in comparison with fresh ones. A total of 667 in vitro fertilisation cycles with fresh or cryopreserved testicular sperm obtained by an open biopsy and testicular needle aspiration were evaluated. Sperm motility was present in 70.9% of the cycles in Group-I, 77.8% cycles in Group-II and in 83.3% In Group-III (NS). The fertilisation rates were similar in the three study groups (50%, 48.6% and 54.8% respectively). The pregnancy rates were 26.7%, 22.2% and 16.3% respectively (NS). The delivery rate, however, was significantly lower in Group-III (4.1%) than in Group-I and -II (18.4% and 15.9%, respectively, P < 0.05). The IVF results after use of cryopreserved testicular sperm are comparable with those obtained with the fresh specimens. Lack of sperm motility before cryopreservation does not exclude favourable outcome and therefore testicular sperm freezing is feasible whenever there are enough sperm cells in the extracted testicular tissue.

A new procedure for removal of a "lost" intrauterine device.

OBJECTIVE: To evaluate the efficacy of removal of a "lost" intrauterine device (IUD) with the use of a cylindrical brush. METHODS: Women aged 25-43 years with so-called "lost" IUD, in whom the string was indiscernible, were enrolled in the study. During gynecologic examination, a cylindrical brush was rotated in the cervical canal until the device was extracted by a rotating motion. No antibiotics were used after removal of the IUD with the cylindrical brush. RESULTS: Twenty-seven women whose IUD could not be removed from the uterine cavity because of an indiscernible string were referred for a trial of IUD removal. All patients had used a plastic, copper-releasing IUD. Before admission, they had undergone an attempt at IUD removal by their physician using either a hook or clamp. In 24 patients who were referred to our center, the IUD was removed by using a cylindrical brush to view the string. The IUD was removed by hysteroscopy in three cases, in two of which no string was found. CONCLUSION: A cylindrical brush can be used safely as an adjunct to remove an IUD and is a simple method that may be performed before another invasive procedure is attempted.

The effect of intracervical vasopressin on the systemic absorption of glycine during hysteroscopic endometrial ablation.

OBJECTIVE: To examine the effect of paracervical injection of vasopressin on the absorption of glycine during transcervical endometrial ablation. METHODS: Thirty-three consecutive women scheduled for elective hysteroscopic endometrial ablation were randomized to either the study or control group. All procedures were performed with a myoma resectoscopy using 1.5% glycine as the irrigating medium at a flow rate of 100 mL/minute. In the study group, a solution of 0.2 mg vasopressin diluted with 20 mL saline was injected paracervically. Blood samples were obtained through an indwelling intravenous catheter every 5 minutes until the completion of the operation. Serum sodium, potassium, and magnesium levels were measured at 20-minute intervals. In addition, glycine concentrations were determined by both rapid screening and quantitative amino acid analysis. RESULTS: Plasma glycine maximal concentrations were significantly lower (P < .001) in patients who received vasopressin, compared with controls (8.8 +/- 4.5 versus 16.0 +/- 6.3 mmol/L, respectively). The calculated extent of glycine absorption within the first 20 minutes of the procedure was 59.6 +/- 30.0 versus 179.8 +/- 66.2 mmol/L.minute in the study and control groups, respectively (P < .001). The differences in plasma sodium, potassium, and magnesium levels were not significant. CONCLUSION: Intracervical vasopressin administration significantly decreased systemic glycine absorption in patients undergoing hysteroscopic endometrial ablation.

Laparoscopic unwinding of twisted ischemic hemorrhagic adnexum after in vitro fertilization.

We present a case where, for the first time, unwinding of ischemic hemorrhagic adnexum was performed successfully through the laparoscope without the need to operate. Aspiration of ovarian fluid before detorsion facilitates the procedure; follow-up showed spontaneous follicular growth. We conclude that laparoscopic detorsion of ischemic adnexum is feasible. Apparently, oocytes are not damaged by the torsion and the ovary resumes normal function. This procedure should be considered in women during the reproductive age and in every case where malignancy can be ruled out.

Treatment of interstitial pregnancy with methotrexate via hysteroscopy.

We present a case in which treatment of interstitial pregnancy with local MTX administration was performed successfully through hysteroscopic vision, without the need to operate. Decreased gestational sac dimension and increased or low beta-hCG level ( < 1,400 mIU/mL) facilitates the success rate. The follow-up showed disappearance of the gestational sac and decrease of beta-hCG levels to < 10 mIU/mL. We conclude that local MTX administration via hysteroscopy after tubal ostium visualization is feasible. The procedure should be considered in women during the reproductive age, especially in rare cases of interstitial pregnancy.

Adnexal torsion of hyperstimulated ovaries in pregnancies after gonadotropin therapy.

A series of 201 cycles of ovarian hyperstimulation syndrome (OHSS) in 154 women were reviewed. Pregnancy occurred in 75 of 201 cycles. Twelve pregnant women (16%) presented with torsion of hyperstimulated ovary, but only 3 out of 126 patients (2.3%) who did not conceive had torsion. Because diagnosis of adnexal torsion is usually uncertain and surgical intervention is likely to be delayed, these infertile women risk losing their ovaries. The clinical picture of torsion of adnexa in patients with OHSS is presented here. The combination of ovarian enlargement, abdominal pain, nausea, progressive leukocytosis, and anemias might indicate torsion of adnexa. Although during operation the adnexa appears dark, hemorrhagic and ischemic, we suggest that it can be saved by simply unwinding it. In 11 such cases intraoperative unwinding of the adnexa was performed, and in 8 patients it was the only operative procedure. No postoperative complications were noted and in all the cases the ovaries were proven functional by ultrasonography. We concluded that torsion of hyperstimulated adnexa in patients who conceived after gonadotropin therapy, is a special entity that requires more attention to achieve early diagnosis. Nevertheless even with delayed diagnosis, the ovary can still be saved.

Ovarian hyporesponsiveness in combined gonadotropin-releasing hormone agonist and menotropin therapy is associated with low serum follicle-stimulating hormone levels.

The study was designed to evaluate if ovarian hyporesponsiveness, which is associated with combined gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) therapy is because of suboptimal serum follicle-stimulating hormone (FSH) levels. Two groups of 12 patients each were suppressed with GnRH-a and stimulation with a fixed dose of hMG. The control group (n = 10) received equal doses of hMG only. The follicular phase and the number of hMG ampules was significantly higher in the study group. Basal FSH levels and FSH levels during hMG treatment were significantly lower in patients treated with GnRH-a. Peak estradiol levels and the outcome of in vitro fertilization treatment were similar in the three groups. We suggest that the delay in ovarian response in patients treated with a combination of GnRH-a and hMG is because of lack of endogenous contribution of FSH, resulting in low circulating levels of FSH. An increase of serum FSH levels by administration of higher doses of hMG can reverse this effect.

Long-term follow-up of the twisted ischemic adnexa managed by detorsion.

OBJECTIVE: To examine our assumption that although the twisted adnexa appears ischemic-hemorrhagic, it can safely be revived by detorsion with preservation of ovarian function. DESIGN: Patients' records were obtained from a computerized database and reviewed. The preoperative diagnosis of adnexal torsion was based upon patients' symptoms, clinical examination, laboratory investigations, and ultrasound scanning. SETTING: Gynecology department at a large teaching hospital receiving primary referrals of public sector patients. PATIENTS: In 40 patients who presented with signs and symptoms suggestive of ovarian torsion, "black-bluish" ischemic adnexa were encountered at surgery. INTERVENTIONS: All patients were managed by unwinding of the adnexa: laparotomy in 26 cases and operative laparoscopy in 14. In 13 patients detorsion only was performed, in 15 detorsion and cystectomy were carried out, and in 12 patients detorsion was done and ovarian cysts aspirated. MAIN OUTCOME MEASURES: Postoperative course, mean hospitalization period, follow-up pelvic examination, ovarian folliculogenesis on ultrasound examination, and oocyte retrieval and fertilization. RESULTS: The size of the twisted ovary ranged from 4 to 20 cm (mean, 9.5 cm). The postoperative course was uneventful, except for transient temperature elevation in five patients. The mean hospitalization period was 6.5 days (range 5 to 10 days) after laparotomy and 1.8 days (range 1 to 3 days) after laparoscopy. Three patients were lost to follow-up. In 37 patients, pelvic examination was normal. A normal sized ovary, with follicular development, was demonstrated sonographically in 35 of 37 patients. In 6 of 7 patients, macroscopically normal adnexa were visualized at subsequent laparotomy or laparoscopy. In two patients undergoing IVF, oocytes were retrieved and fertilized from the detorted ovary. The patency of the fallopian tube was demonstrated in four cases. CONCLUSIONS: This new "adnexal-sparing" approach should be applied instead of the traditional salpingo-oophorectomy in young women with twisted ischemic adnexa.

Cytokine involvement in oocytes and early embryos.

OBJECTIVE: The early events of reproduction involve a carefully modulated complex system of oocyte maturation, fertilization, and proliferation. The aim of the study was to measure the presence of cytokines, namely interleukin 1 (IL-1), interleukin 6 (IL-6), colony-stimulating factor 1 (CSF-1), and tumor necrosis factor (TNF) in the conditioned medium (CM) of the oocytes, granulosa cells, cumulus cells, one to eight-cell embryos and sperm. DESIGN: The material was obtained from men and women undergoing in vitro fertilization therapy. MAIN OUTCOME MEASURES: We hypothesized that cytokines might affect embryonic growth and differentiation as they show a pleotropic effect on immune cells. RESULTS: All these cytokines are present in significant quantities in the CM and were shown to be expressed in a sequential manner; thus, some are present in the oocyte and its vestment, the corona-cumulus complex (IL-1, IL-6, and CSF-1), whereas TNF appears only at the stage of six to eight-cell embryos. Inflammatory cytokines could not be detected in sperm samples. CONCLUSIONS: It is possible that these cytokines have a role in the regulation of embryonic development, maternal immunological recognition of pregnancy, and maintenance of proper hormonal environment.

The effect of gonadotropin-releasing hormone agonist on the ovarian response and in vitro fertilization results in polycystic ovarian syndrome: a prospective study.

OBJECTIVE: To assess the effect of gonadotropin-releasing hormone agonist (GnRH-a) on pituitary suppression, subsequent ovarian response, and results of in vitro fertilization (IVF) treatments in polycystic ovarian syndrome (PCOS) patients. DESIGN: Randomized prospective study. SETTING: In vitro fertilization program and endocrinologic institute. PATIENTS: Thirty patients with PCOS; 16 received GnRH-a, and 14 did not receive GnRH-a. INTERVENTIONS: Ovum pick-up and embryo transfer. MAIN OUTCOME MEASURES: Response to GnRH-a test, serum and follicular fluid (FF) hormonal measurements, steroid levels, and aromatse activity in granulosa cell (GC) culture, and results of IVF. RESULTS: Pituitary responsiveness was abolished in all patients 14 days after GnRH-a administration, and early luteinization was prevented. Steroid levels in FF did not differ between the two groups. In GC culture, progesterone (P) levels were higher in patients without the GnRH-a (3,704 +/- 1,232 nmol/L versus 2,117 +/- 235 nmol/L; P less than 0.05) as were androstenedione (A) levels (5.3 +/- 1.0 nmol/L versus less than 3.5 nmol/L; P less than 0.05). However, aromatase activity and IVF results were similar in the two groups. CONCLUSIONS: Administration of GnRH-a in patients with PCOS decreases P and A production by the GC cells and prevents early luteinization. It does not affect the IVF results.

Outcome of hysteroscopic resection of submucous myomas for infertility.

OBJECTIVE: To examine the reproductive outcome after operative hysteroscopic resection of submucous myomas in women for whom no other infertility factor was identified. DESIGN: Fifteen infertile women with submucous myomas underwent an intensive workup to exclude other causes of infertility. Operative hysteroscopy for resection of the submucous myomas was performed using a rigid 26 French resectoscope (Karl Storz GmbH & Co., Tuttlingen, Germany). SETTING: Academic tertiary referral center. RESULTS: The mean +/- SD duration of the procedure was 25.5 +/- 5.6 minutes. No operative or postoperative complications occurred and all patients were discharged within 6 hours. The follow-up period was 12.0 +/- 4.2 months (mean +/- SD). Seven women conceived (pregnancy rate of 47%) and six of them subsequently delivered at term. CONCLUSION: The results of this study indicate that operative hysteroscopy achieved a pregnancy rate comparable to myomectomy via laparotomy. These results suggest that operative hysteroscopy is the procedure of choice for the resection of submucous myomas in infertile women.

Complete failure of fertilization in couples with mechanical infertility: implications for subsequent in vitro fertilization cycles.

OBJECTIVE: To determine whether complete failure of fertilization of oocytes in couples with mechanical infertility during the first IVF cycle indicates a poor prognosis for subsequent IVF cycles. DESIGN: A retrospective study of 172 cycles of IVF in 50 couples with mechanical infertility and complete failure of fertilization during their first IVF trial. SETTING: In vitro fertilization unit of the Sheba Medical Center. PATIENTS: Fifty couples undergoing one to eight cycles of IVF for mechanical infertility. MAIN OUTCOME MEASURE(S): Fertilization rate of retrieved oocytes and pregnancy rate. RESULTS: Of the initial 50 couples, 44 underwent additional IVF cycles, and 43 (97.7%) achieved fertilization during the second or third cycle. Twenty-four patients conceived during the study period as a result of IVF. CONCLUSIONS: Complete failure of fertilization in couples with mechanical infertility does not necessarily persist during subsequent IVF cycles. Therefore, at least two more IVF cycles should be attempted before reverting to other therapeutic options. Complete failure of fertilization during the first cycle of IVF in couples with mechanical infertility is accompanied by a good prognosis for subsequent cycles.

Complete failure of fertilization in couples with unexplained infertility: implications for subsequent in vitro fertilization cycles.

OBJECTIVE: To determine whether complete failure of fertilization of oocytes in couples with unexplained infertility persists during subsequent in vitro fertilization (IVF) cycles. DESIGN: A retrospective study of 120 cycles of IVF in 44 couples with unexplained infertility and complete failure of fertilization during their first IVF trial. SETTING: In vitro fertilization unit of the Sheba Medical Center. PATIENTS: Forty-four couples undergoing IVF for unexplained infertility. MAIN OUTCOME MEASURE(S): Fertilization rate of retrieved oocytes and pregnancy rate. RESULTS: Of the initial 44 couples, 37 underwent additional IVF cycles and 30 (81.1%) achieved fertilization. Seven patients conceived during the study period as a result of IVF and two conceived spontaneously. CONCLUSIONS: Complete failure of fertilization does not necessarily persist during subsequent IVF cycles. Therefore, at least two more IVF cycles should be attempted before reverting to other therapeutic options. However, although fertilization can be achieved in most couples, the mean oocyte fertilization rate during subsequent cycles in this group is low. This suggests an underlying undiagnosed pathology of oocyte/sperm interaction in some of these patients.

Aromatase activity of human granulosa cells in patients with polycystic ovaries treated with dexamethasone.

The effect of dexamethasone (DEX) (9 alpha-Fluro-16 alpha-methyl prednisolone) on secretion of steroids by human granulosa luteinized cells was studied by culturing cells from mature follicles of women with polycystic ovarian disease and treated for infertility in the in vitro fertilization program. Patients were treated with DEX 0.5 mg/d until the day of human chorionic gonadotropin administration. The cells were cultured for 24 hours in the presence of androstenedione (10(-7)M). After incubating for 24 hours, the medium was replaced and the cells were incubated for an additional 24 hours. The medium was then harvested and assayed for estradiol (E2) and progesterone (P). Results were compared with those of a control group who was not treated with DEX. Estradiol production by cells was significantly lower in the study group treated with DEX. Progesterone production was not influenced by DEX. Follicular fluid levels, E2, and androgens did not vary with DEX treatment, whereas cortisol levels markedly decreased and P levels increased with the treatment. These findings suggest that glucocorticosteroids can directly influence granulosa luteinized cell function.

Follicular and luteal cysts after treatment with gonadotropin-releasing hormone analog for in vitro fertilization.

Ovarian cysts are a common complication of GnRH-a administration. We followed 98 patients who were suppressed with GnRH-a before ovarian stimulation with hMG for IVF treatment. Approximately 20% of the patients receiving GnRH-a during the follicular or luteal phase had developed ovarian cysts. However, the number of cysts per patient was significantly higher in the follicular phase compared with luteal phase. Systematic aspiration of those cysts under local anesthesia permitted the start of ovarian stimulation with hMG as scheduled on day 16 after GnRH-a administration. Follicular fluid content of the cysts revealed similar levels of steroids to those in normal follicles. These cysts contained few cells and no egg. In vitro fertilization treatment was more successful in patients whose cysts were aspirated during the luteal phase than in those with cysts during the follicular phase. We concluded that luteal phase cysts are more benign than follicular phase cysts, and it is possible that they represent an enlargement of pre-existing corpora lutea.

Pituitary and ovarian suppression rate after high dosage of gonadotropin-releasing hormone agonist.

Ten infertile menstruating women were treated with daily injections of gonadotropin-releasing hormone agonist (GnRH-a). The GnRH-a (Buserelin; Hoe 766, Hoechst-AG, Frankfurt/Main, West Germany) was administered subcutaneously (SC) from day 9 of the cycle for 6 days, and intranasally (1.2 mg) for 15 days. Before treatment, all ten women had a normal response to Buserelin challenge test and the GnRH test, and seven of the ten responded to estradiol (E2) benzoate test (2 mg intramuscularly). The SC administration of Buserelin (1.5 mg) for 6 days resulted in suppression of pituitary activity. Continuous treatment with Buserelin (1.2 mg for 3 weeks) was effective as demonstrated by decreasing serum E2 levels to below 20 pg/ml, and in the absence of ovarian follicles in ultrasonographic scanning. Three days after cessation of Buserelin treatment, the pituitary again responded to the GnRH test. Thus, the authors concluded that the administration of Buserelin in very high doses can induce medical hypophysectomy within 6 days, but over 3 weeks of suppression therapy are required to abolish ovarian findings. Desensitization of the pituitary was reversible within 3 days of cessation of the treatment.

Failure to fertilize in vitro in couples with male factor infertility: what next?

OBJECTIVE: To assess the predictive value of a failure to fertilize in vitro in couples with sperm abnormalities on future fertility. DESIGN: Retrospective file review. SETTING: In vitro fertilization and embryo transfer (IVF-ET) program in the Sheba Medical Center during the years 1983 to 1990. PATIENTS: Seventy-six couples with sperm abnormalities who had at least one IVF cycle during which fertilization did not occur. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Occurrence of fertilization, percentage of fertilization, and pregnancies in additional IVF-ET cycles. RESULTS: Of 44 couples who underwent an additional IVF attempt with husband's sperm, 36 (81.2%) fertilized, with a mean fertilization rate of 47.7% +/- 26.6%. Of 17 couples who failed twice, 11 attempted IVF again with husband's sperm and 7 fertilized, with a median rate of 33%. A higher sperm concentration was found on the cycles during which fertilization occurred. Men with single parameter abnormalities did not fertilize better than those with two or three defective parameters. CONCLUSIONS: Failure to fertilize in vitro in couples with male factor infertility does not seem to predict future fertilization in IVF. At least two cycles of IVF should be tried before reverting to other options such as insemination by donor sperm or gamete micromanipulation.

Glucocorticoid administration during transfer of frozen-thawed embryos: a prospective, randomized study.

OBJECTIVE: To establish whether there is any improvement in pregnancy and implantation rates after administration of "low-dose," long-acting glucocorticoids during transfer of cryopreserved-thawed embryos. SETTING: An IVF unit in a university hospital. DESIGN: Prospective, randomized study. Ninety-nine consecutive transfer cycles of frozen-thawed embryos to the uterine cavity of randomly chosen women diagnosed as having tubal factor infertility only. Fifty-two patients underwent transfer of frozen-thawed embryos and received 0.5 mg of dexamethasone; 47 women (control group) did not receive the drug during transfer. PATIENTS: Normal ovulatory patients with tubal factor infertility. INTERVENTIONS: Oral dexamethasone administration before, during and after transfer of thawed embryos. MAIN OUTCOME MEASURES: Pregnancy and implantation rates. RESULTS: The pregnancy rate was 13.5% (7/52) in patients treated with the "low-dose" regimen of dexamethasone compared with 12.8% (6/47) in the control group. The implantation rate was similar. CONCLUSION: Our results demonstrated that the use of 0.5 mg dexamethasone for an immuno-suppressive effect, administered for a short period to patients diagnosed as having "pure" tubal factor infertility, did not improve the implantation or pregnancy rates.

Cytokine levels in follicular fluid of polycystic ovaries in patients treated with dexamethasone.

OBJECTIVE: To assess the levels of cytokines in the follicular fluid of stimulated ovaries. DESIGN: The study included two groups of four patients with polycystic ovarian disease. These were diagnosed by clinical and ultrasonic features and characteristic hormonal profiles, treated with gonadotropin-releasing hormone-analogue and human menopausal gonadotropin. One group received dexamethasone (DEX). MAIN OUTCOME: Dexamethasone is capable of directly affecting granulosa and immune cells. It was also expected to affect cytokine production of granulosa and immune cells of the ovary. RESULTS: This study demonstrates that FF from patients treated with DEX has reduced tumor necrosis factor (TNF) activity and elevated colony-stimulating factor levels. Regardless of the treatment with DEX, the follicles with high levels of TNF contained minimal concentrations of estradiol. Interleukin-6 did not differ between the FF samples. CONCLUSIONS: These results suggest a role for cytokines in the process of folliculogenesis and ovarian maturation. Modification of cytokines by DEX might explain the beneficial effect of fertility.

Outcome of in vitro fertilization and intracytoplasmic injection of epididymal and testicular sperm extracted from patients with obstructive and nonobstructive azoospermia.

OBJECTIVE: To evaluate IVF outcome after epididymal and testicular sperm retrieval in patients with obstructive or nonobstructive azoospermia. DESIGN: Retrospective clinical analysis. SETTING: Public university-affiliated IVF unit. PATIENT(S): One hundred twenty-three azoospermic patients (178 cycles). INTERVENTION(S): Sixty-three patients (103 cycles) with obstructive azoospermia (group 1) underwent either epididymal or testicular sperm retrieval, and 60 patients (75 cycles) with nonobstructive azoospermia (group 2) underwent testicular sperm retrieval combined with IVF treatment. Mature oocytes were fertilized using intracytoplasmic sperm injection. After sperm preparation, supernumerary spermatozoa were cryopreserved. MAIN OUTCOME MEASURE(S): Oocyte fertilization rate and clinical pregnancy rate (PR). RESULT(S): The oocyte fertilization rate was 48.4% (534/1,104) in group 1 and 41.5% (312/751) in group 2 (not significant [NS] difference). A total of 100 cycles (97.1%) and 62 cycles (82.7%) in the obstructive and nonobstructive groups, respectively, had embryos for replacement (NS difference). The clinical PRs per ET cycle were 24% (24/100) and 17.7% (11/62) in the two groups, respectively. Oocyte fertilization rates, when fresh (46.4%) or frozen-thawed (41.8%) spermatozoa were used, were not significantly different in the two groups. The PR when fresh sperm were used was 23.6% (30/127), versus 14.3% (5/35) when frozen sperm were used (NS difference). The PR for women aged < or = 35 years was similar to that for women >35 years of age (20.7% or 29/140 and 18.2% or 4/25, respectively). CONCLUSION(S): Epididymal and testicular sperm obtained in azoospermic patients can fertilize oocytes successfully and may lead to high fertilization rates and PRs. Freezing of these spermatozoa does not reduce the outcome of treatment significantly.