Table of Contents
• AMERICAN ROENTGEN RAY SOCIETY ... Male Infertility: Role of Transrectal Ultrasound (TRUS) in Diagnosis and Management

• AMERICAN UROLOGICAL ASSOCIATION ... The Results of Direct Intracytoplasmic Sperm Injection Using Testicular Sperm

• AMERICAN UROLOGICAL ASSOCIATION ... Human Pregnancies Achieved by Intra-Ooplasmic Injections of Round Spermatid (RS) Nuclei Isolated from Testicular Tissue of Azoospermic Men

• AMERICAN UROLOGICAL ASSOCIATION ... Intracytoplasmic Insertion of Sperm (ICSI) for Severe Male Factor Infertility

• PACIFIC COAST FERTILITY SOCIETY ... Comparative Study Between Two Ovarian Stimulation Protocols: CC/FSH/hMG Versus CC/hMG

• PACIFIC COAST FERTILITY SOCIETY ... Programmed Cycles for Frozen Embryo Transfer: a Simplified Approach

• PACIFIC COAST FERTILITY SOCIETY ... Embryo Implantation After Repetitive Cycles of Oocyte Donation

• PACIFIC COAST FERTILITY SOCIETY ... Treatment of Varicocele: Counselling as Effective as Occlusion of the Vena Spermatica

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According to an abstract presented by the authors to the 95th Annual Meeting of the American Roentgen Ray Society, held April 30 - May 5, 1995, in Washington, D.C., "Purpose: Ultrasound (US) has become crucial in the evaluation of infertile couples, in 50% of whom the male partner is responsible. The purpose of our study is to define the current role of TRUS in the assessment of male infertility caused by abnormalities of the distal reproductive tract. Methods: The study population includes 128 men with azoospermia or oligospermia and low ejaculate volume who were referred for urologic evaluation to our institution during the past 7 years. All patients underwent TRUS using either a General Electric RT 3600 or an ATL Ultramark 9 system. The US findings were correlated with findings on digital rectal examination (DRE) and semen analysis. Results: Sixty patients (46.9%) had congenital bilateral absence of vas deferentia. Twenty (15.6%) had congenital unilateral absence of a vas deferens. In the remaining 48 patients (37.5%) other lesions directly related to semen deficiencies were detected. Thirty-three of them had abnormalities in the seminal vesicles or vas deferentia such as calcifications, cysts, and/or fibrosis. Fifteen had uni- or bilateral ejaculatory duct obstruction caused by cysts, stones or strictures; all of them were correctable by surgery. Conclusions: TRUS enables an accurate diagnosis of certain congenital and acquired anomalies of the lower urogenital tract associated with male infertility. Furthermore, it helps dictate appropriate clinical and surgical management."

According to an abstract presented by the authors to the 90th Annual Meeting of the American Urological Association, held April 23 - 28, 1995, in Las Vegas, Nevada, "Direct intracytoplasmic sperm injection (DICSI) has significantly decreased the minimum sperm density requirements for assisted reproduction. DICSI with ejaculated sperm produces fertilization and pregnancy rates equal to that of conventional in vitro fertilization. Using DICSI in conjunction with microscopic epididymal sperm aspiration has improved fertilization rates per cycle to 100% and pregnancy rates per cycle to 50%. We asked the questions can sperm be successfully harvested from testicular parenchyma and if this is possible what are the fertilization and pregnancy rates when combined with DICSI? Six consecutive couples prospectively underwent six cycles of parenchymal sperm retrieval (PSR) in combination with DICSI. The indications for PSR were bilateral congenital absence of the vas deferens and failed vasal reconstruction. Ovulation induction was carried out using a combined treatment of GnRH agonist and hMG in a short protocol. 0.5 grams of testicular parenchyma was obtained by excisional biopsy. Sperm were retrieved by micromanipulation after incubation of the testicular parenchyma in human tubal fluid. The retrieved sperm were sequentially washed through micro droplets and then injected. This processing yielded an average of 1.2 million sperm per cycle with an average motility of 5%. A total of 72 oocytes were retrieved (12/cycle). DICSI was performed on 59 oocytes, yielding 20 embryos (3.3/cycle). Sixteen embryos underwent uterine transfer (2.7/cycle). The fertilization rate with DICSI using testicular sperm was 100% per cycle. Three ongoing and one full term pregnancy were produced (67%/cycle). The pregnancies consisted of four singletons. Sperm can be successfully retrieved from testicular parenchyma and used to initiate fertilization and pregnancy. Fertilization and pregnancy rates using testicular sperm in conjunction with DICSI are comparable to those using epididymal sperm. Testicular parenchyma can now be utilized as a new reservoir for sperm retrieval in conjunction with DICSI when vasal reconstruction is not feasible."

According to an abstract presented by the authors to the 90th Annual Meeting of the American Urological Association, held April 23 - 28, 1995, in Las Vegas, Nevada, "Successful fertilization and normal embryonic development in vivo after RS nuclear injections (ROSNI) into rabbit oocytes and embryo transfer procedures (J. Urol. 1994, 311A;Fertil. Steril.; In Press) was recently reported. This study evaluates the role of ROSNI in azoospermic men with maturation arrest after the RS stage. Right testicular biopsy was performed in 89 non-obstructed azoospermic men. RS nuclei were isolated in 83 men using methods previously described for rabbit and hamster RS nuclei collection (J. Urol. 1994, 311A;Biol. Reprod. 48:219) and oocytes (n=391) were retrieved from their wives. All oocytes were stimulated mechanically or by a combination of electrical and mechanical stimulation. Then, one husband RS nucleus as microinjected into the corresponding spouse oocyte. A total of 373 oocytes were successfully microinjected and then cultured for 36 hours in BWW medium containing serum at 37(degree)C under 5% CO2. At completion of the culture period 115(31%) 2-to 4-cell stage embryos were transferred to 63 women. Seven weeks following embryo transfer two pregnancies (one twin, one singleton) were identified by ultrasonography. These pregnancies represent 3% (2/63) of the couples in whom embryo transfer was performed and 2% (2/89) of the couples who initially entered the study. The two pregnant women were at the end of the first trimester in October 1994. The etiology of azoospermia in these two ongoing successes were mumps orchitis and varicocele with serum FSH levels of 28 and 23 IU/L, respectively. These results substantiate that ROSNI and subsequent embryo transfer can provide a novel treatment for azoospermic men. These findings further indicate that post-meiotic modifications of the human RS are not required for the pairing of male gamete chromosomes with those of the oocyte."

According to an abstract presented by the authors to the 90th Annual Meeting of the American Urological Association, held April 23 - 28, 1995, in Las Vegas, Nevada, "ICSI has provided an important approach to the treatment of severe male factor infertility. Our results demonstrate that this technique results in a significant enhancement of fertilization rate compared with routine IVF for the male factor patient. At the completion of 70 cycles for 69 couples, 504 oocytes have undergone ICSI, with 400 oocytes surviving (79%). 242 of the 400 surviving oocytes (61%) fertilized normally, while 3% had 3 pronuclei and 2% exhibited activation with 1 pronucleus. 93% of the 70 cycles resulted in embryo transfer with a pregnancy rate of 27% (5 tests are pending). In 16 of the cases, routine IVF was performed in parallel with an average fertilization rate of 33% (n=120 ova). Of note, 23 cycles had less than one million motile sperm prior to processing and in 7 of these the semen analysis could not be performed due to severely impaired semen parameters. For these severely oligospermic patients, the ICSI fertilization rate of 50% was similar to that observed above. One of these patients, considered to be Sertoli cell only based upon a testis biopsy, achieved fertilization and pregnancy with only 14 sperm found in the ejaculate. Similarly, excellent fertilization rates of 50% and 55% were obtained with sperm obtained by electroejaculation (n=4 cycles), and MESA (n=15 cycles). Following in vitro maturation of oocytes (n=14 cycles) and ICSI, or day 2 ICSI for IVF failure (n=15 cycles), the fertilization rates are lower (37% and 34%, respectively). For day 2 ICSI there is also a higher incidence of egg activation and of 3 pronuclei. In our program, the implementation of the ICSI procedure has not only resulted in excellent fertilization rates and embryo transfer rates, but has also enabled us to successfully treat patients whose sperm numbers were too low even for assisted fertilization with subzonal insertion of sperm."

According to an abstract presented by the authors to the 43rd Annual Meeting of the Pacific Coast Fertility Society, held April 26 - 30, 1995, in Coronado, California, "Objective: Induction of ovulation has been accomplished by different stimulatory protocols using clomiphene citrate (CC), human menopausal gonadotropins (hMG) or the combination of both (CC/hMG). Objective: Test if the increase in the follicle stimulating hormone (FSH) at the beginning of the ovulation induction with CC/hMG produces better recruitment and selection of follicles compared with CC/hMG. Design: Prospective comparative study between CC/FSH/HMG (protocol A) vs. CC/HMG (protocol B), from January to December 1993. Material and Methods: Blood determination of FSH, luteinizing hormone (LH), estradiol (E(2)), prolactin (PRL) and transvaginal ultrasound (TUS) were done on day 3 of the cycle. Based on these results induction was initiated. 50 mg of CC was given from day 5 to day 9 of the cycle. Patients in the first protocol received 75 IU of FSH (Fertinorm, Serono, Mexico) on days 6, 7, 8 of the cycle. Patients in the second protocol received 75 IU of FSH/LH (Pergonal, Serono, Mexico). FSH was changed to 75 IU hMG when E(2) reached levels higher than 260 pg/mL. 10,000 IU of human chorionic gonadotropin (hCG) when at least one follicle measured 16 mm. E(2) and progesterone (P4) were drawn 9 days after hCG. Results: 288 cycles were included in this study, 117 cycles in protocol A and 171 cycles in protocol B. No statistical difference was seen between the groups in: age, duration of infertility, diagnosis, FSH/LH ratio on day 3 of cycle, in ranges of age. (P(greater than).05). We observed consistently better response in protocol A demonstrated by a higher number of follicles (greater than)15 mm, higher E(2) at hCG administration, thicker endometrium and higher P4 levels. When analyzed by diagnosis, protocol A produced a statistical better response (p{{(less than)=}}0.05) than protocol B in patients with endometriosis, polycystic ovaries and unexplained infertility. Pregnancy rate in protocol A was 17.9% vs. 9.9% in B. Conclusion: the addition of FSH in the CC/HMG protocol induces an increment in the recruitment and maturation of follicles."

According to an abstract presented by the authors to the 43rd Annual Meeting of the Pacific Coast Fertility Society, held April 26 - 30, 1995, in Coronado, California, "With improvement in cryopreservation techniques, replacement of frozen embryos is increasingly utilized for the attainment of pregnancy. In order to maximize endometrial receptivity and allow elective scheduling of frozen embryo transfers (FET), GnRH analogs such as leuprolide acetate (LA) have been used to down regulate the hypothalamic-pituitary-ovarian axis prior to stimulation of the endometrium by exogenous estrogens and progestins. The use of LA, while successful, necessitates 2 to 3 weeks of injections and is accompanied by the cost of the LA. The purpose of this study was to investigate the utility of a regimen of exogenous oral estradiol (E) and IM progesterone (P) commencing with spontaneous menses as compared with LA down regulation prior to hormone replacement (HRT) in the success of FETs. Since we have previously shown that exogenous E alone does not prevent ovulation, a serum P level was obtained prior to starting supplemental P. Between January 1, 1994, and October 31, 1994, a total of 77 frozen embryo replacement cycles were undertaken. In 43 cycles, the patients received only E and P (E/P), while in 34 cycles, the patients were treated with LA, followed by E and P (L/E/P). A total of 166 and 126 embryos were replaced in the E/P and L/E/P groups respectively, with a mean of 3.95 and 3.82 embryos per transfer in each of the two groups. No significant differences in implantation rates per embryo (7.2% vs. 11.1%) were noted in the E/P and L/E/P groups. When we subdivided each group by the source of the oocytes (patient or donor), there was again no significant difference between the two groups (for patient oocytes: 5.1% (5/99) vs. 0% (0/14) and donor oocytes: 10.5% (7/67) vs. 12.5% (14/112) for the E/P and L/E/P group respectively). There was no difference in the clinical pregnancy rate per transfer (23.8% vs. 26.5%) between the two groups. The source of the oocytes did not significantly affect outcome (patient oocytes: 22.7% (5/22) vs. 0% (0/6), donor oocytes 24% (6/24) vs. 32% (9/28) for E/P and L/E/P respectively. One cycle in the E/P group (2.4%) was cancelled due to premature ovulation. The E/P regimen required significantly less days (31 vs. 14) prior to transfer and was less costly ($263 vs. $586) than the L/E/P regimen. We conclude that an artificial regimen for FET utilizing solely estradiol and progesterone is as efficacious, less costly, and easier to administer than a regimen which utilizes a GnRH analog prior to hormonal supplementation."

According to an abstract presented by the authors to the 43rd Annual Meeting of the Pacific Coast Fertility Society, held April 26 - 30, 1995, in Coronado, California, "Oocyte donation (OD) is now a well-established modality in the treatment of infertility among women with poor oocyte quality or among those who do not wish to reproduce a genetic defect. Because of the simultaneous optimization of both embryo quality and endometrial receptivity, OD consistently produces the highest per embryo implantation rates (IRs) of the assisted reproductive techniques. To investigate whether success rates decrease with repetitive cycles, we analyzed up to the first 4 cycles in 287 recipients of OD performed at our institution with respect to clinical IRs and delivery rates (DRs). For cumulative pregnancy analyses, only the cycles prior to and including the first cycle producing either a clinical pregnancy or a delivery were considered and the remaining cycles of that recipient censored. In this manner, 397 cycles were observed to result in 134 clinical pregnancies (33.8%, 95% C.I., 30-38%). Per cycle IRs were 13.9% (169/1219), 9.3% (35/376), 7.6% (8/105), and 31.6% (6/19) for cycles 1-4, respectively while the per cycle PRs were: 35.9% (103/287), 24.7% (21/85), 38.1% (8/21), and 50% (1/2) for cycles 1-4, respectively. Cumulative PRs by life-table analysis were: 35.9%, 51.7%, 70.1 % and 85.1% for cycles 1-4, respectively. Analysis of DRs revealed 112 total deliveries in 419 evaluable cycles (26.7%, 95% C.I., 23-31%). Per cycle ongoing IRs (babies per embryos transferred) were 11.2% (136/1219), 7.4% (28/376), 6.7% (7/105), and 26.3% (5/19) for cycles 1-4, respectively, while the per cycle DRs were 27.9% (80/287), 21.1% (20/95), 28.0% (7/25), and 62.5% (5/8) for cycles 1-4, respectively. Cumulative DRs were: 27.9%, 43.1%, 59.0%, and 84 6% for cycles 1-4, respectively. No decrease in per cycle IRs, PRs or DRs was observed. We conclude that 1) no decrease in IRs, PBs or DRs is observed in up to 4 cycles of OD, and 2) OD produces high cumulative success rates with a greater than 80% delivery rate after 4 cycles."

According to an abstract presented by the authors to the 43rd Annual Meeting of the Pacific Coast Fertility Society, held April 26 - 30, 1995, in Coronado, California, "Occlusion of the vena spermatica is generally accepted as the treatment of choice in infertile patients with idiopathic varicocele. Recently, we demonstrated that surgical ligation or radiological embolization of the vena spermatica are equally effective in terms of pregnancy rates following treatment [Nieschlag et al. (1993):Andrologia 25, 233-237]. However, it remained unclear whether any treatment at all is more effective than no treatment. The current study was initiated to address this question. Materials and Methods: Infertile patients with varicocele were investigated at least twice, including Doppler sonography, ultrasonography of the scrotal contents, continuous scrotal temperature recording over 24 h, semen analysis according to WHO guidelines and hormone measurements. Other pathologies possibly leading to infertility were excluded and the patients' wives had to be free of obvious causes of infertility such as anovulation or tubal blockage. The patients fulfilling the admission criteria were randomly allocated to groups receiving either treatment (ligation or embolization) or no treatment. Thereafter, all patients were investigated and counselled every 3 months over 1 year. Results: In total, 47 couples in the treatment group (23 ligations and 24 embolizations) and 49 in the non-treatment group concluded the study. During the 1 year observation period, 14 pregnancies (28%) were recorded in the treatment group and 15 (31%) in the non-treatment group. Conclusions: These results challenge the current approach to the management of varicocele patients and emphasize the need for controlled studies in infertility treatment."