Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men.

PURPOSE: Finasteride, an oral type 2, 5alpha-reductase inhibitor, is used in 1 mg. daily doses for the treatment of male pattern hair loss. A dose of 5 mg. finasteride daily reduces ejaculate volume by approximately 25%, and reduces prostate volume by approximately 20% and serum prostate specific antigen (PSA) by approximately 50% in men with benign prostatic hyperplasia. To our knowledge no data exist on the effect of 1 mg. finasteride daily on ejaculate volume or other semen parameters, or on the prostate in young men. Therefore, we studied the potential effect and reversibility of effect of 1 mg. finasteride daily on spermatogenesis, semen production, the prostate and serum PSA in young men. MATERIALS AND METHODS: In this double-blind, placebo controlled multicenter study 181 men 19 to 41 years old were randomized to receive 1 mg. finasteride or placebo for 48 weeks followed by a 60-week off-drug period. Of the 181 men 79 were included in a subset for the collection and analysis of sequential semen samples. RESULTS: There were no significant effects of 1 mg. finasteride on sperm concentration, total sperm per ejaculate, sperm motility or morphology. Ejaculate volume in subjects on finasteride decreased 0.3 ml. (-11%) compared to a decrease of 0.2 ml. (-8%) for placebo, with a median between treatment group difference of -0.03 ml. (1%, 90% confidence interval -10.4 to 13.1, p = 0.915). There were significant but small decreases in prostate volume (-2.6%) and serum PSA (-0.2 ng./ml.) in the finasteride group, which reversed on discontinuation of the drug. CONCLUSIONS: Treatment with 1 mg. finasteride daily for 48 weeks did not affect spermatogenesis or semen production in young men. The effects of 1 mg. finasteride daily on prostate volume and serum PSA in young men without benign prostatic hyperplasia were small and reversible on discontinuation of the drug.

Continuation of a donor oocyte pregnancy in a functionally agonadal patient without early oestrogen support.

A 40 year old functionally agonadal patient was the recipient of fertilized donated oocytes. She accidentally discontinued all oestrogen support on the day preceding embryo transfer until it was reinstated 12 days later. However, a pregnancy was established and resulted in the birth of healthy normal twin infants. This case report suggests that minimal amounts, if any, of oestradiol are sufficient to maintain an early pregnancy, provided adequate amounts of progesterone are given. This is consistent with a recent study conducted in subhuman primates.

Treatment options for infertile couples.

Fast-developing technologies in infertility treatment make it a prime subject for review. In this paper, we revisit some of the basic biology of the male and female reproductive systems and point out where these systems break down. We then discuss some of the many technical treatment options available for the infertile couple and indicate where and when these technologies are best applied.

A novel ovarian stimulation protocol for use with the assisted reproductive technologies.

OBJECTIVE: To determine whether a new ovarian stimulation protocol termed "minimal stimulation" provides pregnancy rates (PRs) comparable with those in a conventional full stimulation protocol for patients undergoing assisted reproductive technologies (ART). DESIGN: Prospective, nonrandomized study of patients in minimal stimulation or full stimulation, followed by standard IVF and zygote intrafallopian transfer or uterine-ET. SETTING: The ART program of the Mayo Clinic, Rochester, Minnesota. PATIENTS: Women (n = 120) 42 years of age or younger with serum day 3 FSH level < or = 15.0 mIU/mL (conversion factor to SI unit, 1.0), normal thyroid-stimulating hormone and PRL levels, normal endometrial cavity as observed on hysterosalpingogram, and partners with a normal semen analysis. INTERVENTIONS: Oral clomiphene citrate, hMG, oocyte retrieval, IVF-ET. MAIN OUTCOME MEASURES: Cancellations, implantation, pregnancy. RESULTS: The cancellation rate was not significantly higher in minimal stimulation (25.8%) than in full stimulation (14.1%). Minimal stimulation cycles yielded fewer oocytes per aspiration (3.4 +/- 1.6) than full stimulation (10.1 +/- 5.4). There was no difference in the implantation rates per ET (minimal stimulation, 16.4%; full stimulation, 13.3%) or overall clinical PRs per retrieval (minimal stimulation, 31%; full stimulation, 42%). CONCLUSIONS: Minimal stimulation for IVF is less expensive than full stimulation and minimizes monitoring and patient discomfort. In addition, it produces acceptable PRs and represents an attractive alternative to select patients undergoing ART.

A successful assisted reproductive technology satellite program.

A satellite program was implemented to provide IVF to interested infertile couples living in a five-state area. Thirty-six gynecologists were established as satellite sites after appropriate screening and training. No attempt was made to interchange reference serum specimens between laboratories. Patients were seen at Mayo Clinic for an initial consultation and did not return until the ovulatory dose of hCG was administered. There was no difference in cancellation, clinical pregnancy, and delivery rates between satellite and central unit monitored patients. Satellite monitoring decreases patient inconvenience and time away from home and the workplace without compromising cycle outcome.

The multicentre transcervical balloon tuboplasty study: conclusions and comparison to alternative technologies.

Transvaginal tubal catheterization procedures have been suggested as an alternative to microsurgery and in-vitro fertilization (IVF) in the treatment of women with proximal tubal occlusion. A transcervical balloon tuboplasty (TBT) catheter was specifically developed and tested in a prospective multicentre trial. A total of 151 women with confirmed bilateral or unilateral tubal occlusion were studied. The primary study population included 106 women who, after exclusion of patients for protocol violations, represented those females who were treated for complete tubal occlusion with TBT. TBT is an ambulatory, minimally invasive catheter procedure, performed under paracervical block or mild sedation, which utilizes a co-axial balloon catheter under fluoroscopic guidance. Re-canalization, pregnancy and reocclusion rates following the procedure were documented. A total of 28 patients demonstrating uni- or bilateral tubal patency after either hysterosalpingography and/or selective salpingography represented the control population. TBT established tubal patency of at least one Fallopian tube in 95/106 patients (90%) and in 167/205 obstructed oviducts (82%). Clinical pregnancies occurred in 37/106 females (35%), with a life table adjusted rate of 37%. Patients without distal disease had significantly higher pregnancy rates than those with bipolar tubal disease (49% versus 12%, life table adjusted rate; P = 0.0002) but pregnancy rates were independent of underlying aetiology for tubal disease. Pregnancy rates in control patients who did not reach TBT because of tubal patency after hysterosalpingography and/or selective salpingography were significantly lower than in those successful treated with TBT (P = 0.027), and occurred only for four cycles after hysterosalpingography and with approximately a 1 year delay after selective salpingography.(ABSTRACT TRUNCATED AT 250 WORDS)

Falloposcopy.

This review discusses advances in falloposcopy over the past 10 years. Refinements in instrumentation, including fiberoptics, have allowed visualization of the endosalpinx, a portion of the reproductive tract that has evaded endoscopic evaluation. A coaxial system of falloposcopic placement may give way to a linear everting catheter that does not require hysteroscopic guidance. Tubal endoscopic applications are discussed, including correlating hysterosalpingogram findings with those findings at salpingoscopy. Endosalpingeal changes can be quantitated in the presence of hydrosalpinges, and possibly with endometriosis. A scoring system to measure changes has been described. Using this scoring system, endosalpingeal findings at salpingoscopy have been compared with histologic and electron microscopic findings.

Advances in gynecologic imaging and intervention.

Advances in diagnostic imaging of the female genital tract facilitate characterization of many pelvic masses. Preoperative assessment of gynecologic malignant tumors provides information that may alter the surgical approach or timing of radiation therapy. Image-guided biopsy accurately confirms recurrent malignant lesions. Transcervical techniques have improved diagnostic assessment of infertile couples; thus, effective and inexpensive treatment options can be offered. Postoperative complications of gynecologic procedures can be detected with imaging, and many can be treated with image-guided techniques.

Laparoscopic use of sutures.

The ability to do laparoscopic suturing or stapling techniques effectively greatly adds to the level of comfort and performance of the endoscopic surgeon. Each of us is driven by the desire to do a given procedure at laparoscopy just as well as we could at laparotomy. If we cannot, we question whether or not it should be done endoscopically by us. By being able to perform the techniques just described, surgeons can deal effectively with many situations which might otherwise keep them from providing an endoscopic service to their patients. Finally, we must weigh carefully the pros and cons of placing any sutures at all in a given situation.

Transcervical balloon tuboplasty. A multicenter study.

Transcervical balloon tuboplasty represents a noninvasive technique to treat proximal tubal occlusion. In a multicenter study, 77 women with confirmed bilateral proximal tubal occlusion underwent the procedure. In 71 patients (92%), at least one proximally obstructed fallopian tube was recanalized. Concomitant distal bilateral tubal occlusions were diagnosed after successful proximal tubal balloon recanalizations in 13 patients (17%). In the remaining 64 patients, 22 clinical pregnancies (34%) have been confirmed during a median follow-up period of 12 months. Among those, 17 (77%) resulted in normal deliveries and five (23%) resulted in a first-trimester miscarriage. One patient was diagnosed with an ectopic pregnancy. Among 25 patients who had not conceived within 6 months of the procedure, 17 (68%) demonstrated continuing tubal patency on repeated hysterosalpingogram. We conclude that transcervical balloon tuboplasty is a safe outpatient technique that may represent an alternative to in vitro fertilization or microsurgical reanastomosis of fallopian tubes.

Cocaine use and acute rupture of ectopic pregnancies.

The hemodynamic changes associated with ingestion of cocaine may precipitate rupture of ectopic pregnancy. Two cases are presented in which this association was suspected. We believe this to be the first report of this clinical entity, representing a risk factor that should be identified in patients with suspected ectopic pregnancy.

Endometriosis-associated infertility. Treatment options.

Formulating a treatment plan for infertility associated with endometriosis is difficult due to the lack of a cause-and-effect relationship between the disease and infertility. Several molecular and cellular mechanisms have been postulated as playing roles in endometriosis-associated infertility; they are reviewed here. Several medical and surgical treatment options are discussed, including danocrine, medroxyprogesterone acetate and gonadotropin releasing hormone agonists. A combined medical and surgical approach and occasional expectant management remain the treatments of choice.

Indications for hysteroscopy.

A description of current indications for hysteroscopy is presented, including a review of the literature. Emphasis is placed upon indications that are felt to be useful in the diagnosis and treatment of common gynecologic problems, including abnormal uterine bleeding, infertility, recurrent pregnancy wastage, and removal of intrauterine foreign bodies.

Analysis of chromatin proteins from human placenta.

Low-salt extracts of chromatin from human term placenta have been examined for the presence of the high mobility group (HMG) proteins. Based upon salt-dissociation characteristics, solubilities in trichloroacetic acid and electrophoretic behaviour on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and non-equilibrium pH gradient gel electrophoresis (NEPHGE), each of the HMG proteins is present, including HMG-1, -2, -E, -14, and -17. A remarkably large amount of HMG-E is present in term human placenta. Additionally, a protein not previously recognized, which we designate HMG-PL, is present in term placenta. Electrophoretic comparison of the HMG proteins from placentae of varying gestational age, using NEPHGE, demonstrates that all of the placental HMG proteins exhibit multiplicity, reminiscent of chicken erythrocyte HMG proteins. Specifically, we found HMG-E to be unaltered in amounts relative to HMG-1 and -2 in placentae varying from 20 to 40 weeks of gestation. HMG-PL, however, is differentially expressed, increasing in amounts as gestation proceeds past 34 weeks. HMG-PL was purified and subjected to amino acid analysis. Its composition supports the notion that HMG-PL is a member of the HMG-1 family.

Amino acid sequence and secondary structural analysis of the corn inhibitor of trypsin and activated Hageman Factor.

The amino acid sequence of a corn inhibitor for trypsin and activated Hageman Factor (Factor XIIa) was determined by automated Edman degradation from the intact inhibitor and two fragments generated by specific cleavage of the inhibitor. The 112-residue sequence is unique at each position except 91, where both Ala and Glu were found. The structural heterogeneity suggests the occurrence of two genes (possibly allelic) for the inhibitor. Based on analysis of fragments produced by the interaction of the inhibitor with trypsin-agarose, the reactive site peptide bond is identified as Arg 36-Leu 37. There is no strong similarity between the sequence of the corn inhibitor and the sequences published for other serine protease inhibitors. Thus, the corn inhibitor represents a new family of protease inhibitors. Circular dichroism measurements and a theoretical prediction of secondary structure indicate that the inhibitor has helix and beta sheet contents of approximately 40 and 20%, respectively.