Robert L. Collins

Efficacy of a gonadotropin-releasing hormone agonist in the treatment of uterine leiomyomata: long-term follow-up *

The authors employed a gonadotropin-releasing hormone agonist (GnRH-a) (D-His6-pro9-NET-GnRH) to treat 19 patients with symptomatic uterine leiomyomata, by daily subcutaneous injections (4 micrograms/kg) for 6 months. After therapy, patients were followed for 6 months without any therapy. Uterine volumes were measured by serial pelvic examinations and pelvic sonography. Measurements of serum estradiol, luteinizing hormone, and follicle-stimulating hormone were used to assess treatment response. Pituitary desensitization and hypoestrogenemia were achieved in all within 8 weeks, and in 18 of 19, hypoestrogenemia was maintained for the duration. Uterine volume at the conclusion of therapy (207.5 +/- 152.7 ml) was significantly reduced in all patients when compared with pretreatment sizes (420.8 +/- 276.4, P less than 0.05). Side effects included hot flashes (78%), vaginal dryness (32%), and transient frontal headaches (55%). All patients reported partial or complete relief from their symptomatic leiomyomata. Uterine volume at the conclusion of follow-up (345.4 +/- 195.7 ml) was greater than at the conclusion of therapy. Menses resumed in all patients within 4 to 8 weeks. In conclusion, GnRH-a therapy does not provide definitive therapy for symptomatic uterine leiomyomata but is effective in reducing the size of leiomyomata as a temporary measure. Gonadotropin-releasing hormone agonist therapy may be useful as an adjunct before myomectomy or hysterectomy and deserves further investigation.

The effect of intraperitoneal progesterone on postoperative adhesion formation in rabbits.

The immunosuppressive and anti-inflammatory properties of progesterone (P) have been established. The authors investigated whether the intraperitoneal instillation of P would lessen postoperative adhesion formation in New Zealand white rabbits undergoing pelvic surgical procedures. In phase I, severe, peritoneal lesions were made in the right uterine horn (n = 48). Animals were randomized to receive equal volumes of either (1) Ringers lactate (RL); (2) 32% dextran 70 (HY; Hyskon Division, Pharmacia, Piscataway, NJ); (3) 500 mg P in oil (PO); or (4) 500 mg aqueous P (PA) at initial laparotomy. In phase II, the distal right uterine horn, including the mesosalpinx, was excised and microsurgical anastomosis was accomplished (n = 45). Aqueous P was not used in phase II; otherwise, the same agents were tested. Six weeks later, the severity of the adhesions formed was graded. The mean adhesion scores for the RL and HY groups were low for the right side in both phases and did not differ (P greater than 0.05). In contrast, higher scores were observed in all the P groups, regardless of the P preparation used or the surgical procedure performed (P less than 0.05).

A case study in cross-talk: the histone lysine methyltransferases G9a and GLP

The histone code hypothesis predicts that the post-translational modification of histones can bring about distinct chromatin states, and it therefore serves a key regulatory role in chromatin biology. The impact of one mark on another has been termed cross-talk. Some marks are mutually exclusive, while others act in concert. As multiple marks contributing to one outcome are generally brought about by complexes containing multiple catalytic and binding domains, it appears regulation of chromatin involves a web of writers and readers of histone modifications, chromatin remodeling activities and DNA methylation. Here, we focus on the protein lysine methyltransferases G9a and GLP as examples of this extended cross-talk. G9a and GLP can catalyze the formation of and bind to the same methyl mark via distinct domains. We consider the impact of other histone modifications on G9a/GLP activity and the coordination of activities within G9a/GLP containing complexes. We evaluate the potential impact of product binding on product specificity and on maintenance and propagation of the methyl mark. Lastly, we examine the recruitment of other silencing factors by G9a/GLP. Regulated assembly of specific complexes around key marks may reinforce or alter the biological outcome associated with given histone modifications.

Current concepts of β-endorphin physiology in female reproductive dysfunction

beta-Endorphin has a role in the regulation of the normal menstrual cycle and possibly in the onset of puberty. We have reviewed the evidence pointing to an alteration in this neuropeptide that may contribute to the pathogenesis of various reproductive dysfunctions. Elevated or high levels of beta-endorphin have been associated with exercise-associated amenorrhea, stress-associated amenorrhea, and polycystic ovarian syndrome. Depressed or low levels of beta-endorphin have been associated with PMS and menopause. Alterations in the levels of beta-endorphin may change the pulsatile release of GnRH via noradrenergic and/or dopaminergic pathways. We have primarily focused on beta-endorphin as representative of the endogenous opioid peptides, but other opioid peptides may also contribute to the pathogenesis of various types of reproductive dysfunction. Perhaps it will become possible to characterize and hone our understanding of the function of beta-endorphin and the other substances composing the endogenous opioid peptides. A better understanding of their role in physiological as well as pathophysiological processes may allow for the development of rational approaches to the treatment of specific disorders pertaining to reproduction. Many questions remain unanswered. Among the most relevant are: what is the precise mechanism of action by which beta-endorphin exerts its influence on pulsatile GnRH release? Is there a functional relationship between CNS and peripheral (serum) levels of beta-endorphin? Are the detected changes in beta-endorphin levels merely associated, or are they a cause of a particular disorder? Since it took almost 40 years between the time prostaglandins were first discovered and eventual realization of their clinical application, it may take some time before the beta-endorphin story is complete.

Office-Based Infertility Practice

SECTION I - Evaluation and Practice: Introduction 1. Evaluation of the Female 2. Evaluation of the Male 3. Detection and Therapeutic Approaches to Age Related Infertility 4. The Role of Ultrasound in Infertility 5. Coping with Infertility: Practical Psychosocial Issues 6. The Impact of Managed Care on Office Based Infertility Practice. SECTION II - Procedures: 7. Basics of the Laboratory Set-Up in the Office 8. Office Anesthesia 9. Ovulation Induction and IUI 10. Diagnostic and Therapeutic Hysteroscopy 11. Endoscopic Evaluation of the Fallopian Tubes 12. Transcervical Tubal Cannulation 13. Office Minilaparoscopyfor Infertility 14. Cervical Stenosis 15. Office Treatment of of Male Reproductive Function 16. Routine IVF in the Office Setting 17. Unstimulated IVF and In-Vitro Oocyte Maturation 18. Intratubal Gamete Transfer 19. Complications of Ovulation Induction.

Outcome of laparoscopic versus traditional surgery for ectopic pregnancies**Presented at the Annual Meeting of the Pacific Coast Fertility Society, Indian Wells, California, April 11 to 14, 1991.†Department of Gynecology.

OBJECTIVEnTo compare pregnancy rates after three surgical procedures for ectopic pregnancy (EP) over a 9-year period for normal and infertility patients.nnnDESIGNnIn a retrospective analysis, we examined crude pregnancy rates and life-table analysis of cumulative pregnancy rates. A proportional hazard regression model was used to examine relative risk of type of surgery and fertility rates.nnnPATIENTS, PARTICIPANTSnOne hundred twenty-six cases of EPs were reviewed at the Cleveland Clinic Foundation, a tertiary institution.nnnMAIN OUTCOME MEASURESnComparisons of rates of viable term deliveries were calculated between three types of surgery and were stratified according to the status of infertility. Confidence intervals for relative risk of surgery and fertility status on future pregnancy were calculated.nnnRESULTSnNo difference in pregnancy rates was observed after the three procedures (P = 0.08). Normals had a significantly higher (4 times higher) pregnancy rate than infertility patients, independent of surgical procedure.nnnCONCLUSIONnSuccessful pregnancy after EP is related to history of infertility rather than type of surgery to treat ectopic event. More randomized study is needed to examine laparoscopic salpingostomy, especially in patients with other infertility problems.