Bleeding profile and endometrial safety of continuous combined regimens 1 mg 17beta-estradiol/trimegestone versus 1 or 2 mg 17beta-estradiol/norethisterone acetate in postmenopausal women.

OBJECTIVE: To compare the bleeding profile and endometrial safety of continuous combined 1 mg 17beta-estradiol (17beta-E2) and 0.125 mg trimegestone (TMG) with those of two continuous combined 17beta-E2 and norethisterone acetate (NETA) regimens. STUDY DESIGN: This was a double-blind, randomized, multicenter study conducted in 12 European countries and Israel over a 2-year period. Healthy postmenopausal women with an intact uterus were given either 1 mg 17beta-E2/0.125 mg TMG, 2 mg 17beta-E2/1 mg NETA or 1 mg 17beta-E2/0.5 mg NETA for up to 26 cycles, each of 28 days. RESULTS: The percentage of amenorrheic women was greater in most cycles up to cycle 13 in the 1 mg 17beta-E2/0.125 mg TMG group than in the comparator groups. The mean number of bleeding days was similar in the 1 mg 17beta-E2/0.125 mg TMG and the 1 mg 17beta-E2/0.5 mg NETA groups, but greater in the 2 mg 17beta-E2/1 mg NETA group. No endometrial hyperplasia was observed for any group. CONCLUSION: Continuous combined 1 mg 17beta-E2/0.125 mg TMG exhibits a more favorable bleeding profile than 1 mg 17beta-E2/0.5 mg NETA up to 1 year, while providing an adequate protective effect on the endometrium.

Laparoscopic myomectomy in premenopausal women with and without preoperative treatment using gonadotrophin-releasing hormone analogues.

The present study was undertaken in order to evaluate the usefulness or otherwise of preoperative gonadotrophin-releasing hormone (GnRH) analogue treatment prior to laparoscopic myomectomy. From June 1993 through December 1996, 60 premenopausal women aged between 25 and 42 years and with a sonographic diagnosis of intramural or subserous myomas were selected for laparoscopic myomectomy at the Department of Obstetrics and Gynaecology of the Catholic University of The Sacred Heart, Rome. According to a computer-generated sequence, 30 patients were submitted to three cycles of GnRH analogue treatment prior to surgery, whereas no preoperative treatment was prescribed to the other 30 patients. Laparoscopic myomectomy was successfully performed in all patients for a total of 174 myomas excised laparoscopically. The patients' mean age, the number of myomas per patient, the mean diameter of the myomas, parity and estimated blood loss were similar in both groups. The operative time was significantly longer in the group of patients submitted to GnRH analogue treatment than that of the group of patients not submitted to any preoperative medical therapy (157.5 +/- 74.71 versus 112.33 +/- 54.71 min; P = 0.01). No intra-operative complications occurred. In no case was blood transfusion necessary. Two patients developed post-operative fever (temperature > 38 degrees C.). The mean length of hospital stay was 2.39 days and was similar in both groups. Thirteen spontaneous pregnancies occurred among 24 infertile patients (54.1%). The pregnancy rate for these patients was similar in both groups. The viable term delivery rate was 45.8%. The authors conclude that laparoscopic myomectomy is a feasible and safe procedure. The post-operative pregnancy rate for infertile patients is similar to that following laparotomic myomectomy. The present study suggests that preoperative GnRH analogue treatment does not offer any significant advantages for laparoscopic myomectomy.

Laparoscopically assisted vaginal hysterectomy versus total abdominal hysterectomy: a prospective, randomized, multicenter study.

OBJECTIVE: The objective of this study was to evaluate short-term results of laparoscopically assisted vaginal hysterectomy with those of total abdominal hysterectomy in a prospective, randomized, multicenter study. STUDY DESIGN: One hundred sixteen patients referred for abdominal hysterectomy were randomized to either laparoscopically assisted vaginal hysterectomy (58 patients) or abdominal hysterectomy (58 patients). Inclusion criteria were one or more of the following, where a vaginal hysterectomy would be traditionally contraindicated: uterine size larger than 280 g, previous pelvic surgery, history of pelvic inflammatory disease, moderate or severe endometriosis, concomitant adnexal masses or indication for adnexectomy, and nulliparity with lack of uterine descent and limited vaginal access. An upper limit of uterine size was set at 16 weeks' gestation (ie, 700 g). RESULTS: There were no differences in terms of patient's age, parity, preoperative hemoglobin levels, mean uterine weight, and total operating time between the 2 groups. Estimated blood losses and postoperative day 1 hemoglobin drop were significantly lower for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy (P<.05). There were 1 major and 2 minor complications in the laparoscopically assisted vaginal hysterectomy group compared with 2 major and 5 minor complications in the abdominal hysterectomy group (P not significant). Postoperative pain was lower for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy on postoperative days 1, 2, and 3 (P<.05). Postoperative hospital stay was significantly shorter for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy (P<.001). CONCLUSIONS: The present study demonstrates that, given adequate training in laparoscopic surgery, laparoscopically assisted vaginal hysterectomy may replace abdominal hysterectomy in most patients who require a hysterectomy and have contraindications to vaginal hysterectomy, with all the benefits associated with the vaginal route.

[The ICSI (Intracytoplasmic Sperm Injection)]. / La ICSI (Intracytoplasmic Sperm Injection).

ICSI (Intracytoplasmic Sperm Injection) is the latest known assisted reproduction technique (ART) and it already appears to be mature. In fact the analysis of the results presented by the researchers over the years has shown that the most specific indication for this ART is the sterility of the couple with serious male pathology, up to ejaculatory azoospermia where it is possible to perform MESA, PESA or TESE. Any kind of sterility could be solved with ICSI whose only limit presently known is the high technology and therefore high costs involved. The percentage of oocytes that undergo ICSI without being damaged varies from 87% to 94% and the percentage of fertilization varies from 33% to 71%. The transfer rate is 59-100%. The rate of pregnancies per couple ranges from 12% to 40% of the couples, from 11% to 41% for the transfers. Since abortions are similar to the values of the normal population (10-15%), ICSI is actually the assisted fertilization technique with the highest incidence of pregnancies and "take home babies". The percentage incidence of the two sexes, of the malformations and the typologies of malformations corresponds to those observed in the population with spontaneous pregnancies. Since there is no natural selection of the gametes in ICSI, one may be sure that when spermatozoa with any kind of pathology are injected, the pregnancy does not take place at all.

Spontaneous pregnancy after 13 years of amenorrhea in a patient with a voluminous ovarian dysgerminoma and submitted to left adnexectomy and radiotherapy.

The authors illustrate the case of a 17-year-old patient who was submitted to left adnexectomy in view of an ovarian dysgerminoma 24 cm in diameter and weighing 2,800 g. She was subsequently submitted to two cycles of radiotherapy. Following a period of amenorrhea lasting 13 years and characterized by high serum levels of gonadotropins, the patient had a spontaneous pregnancy and at 33 weeks of gestation delivered a live and vital fetus. Therefore the occurrence of post-radiotherapy amenorrhea, characterized by high serum gonadotropin levels, should not always be considered pathognomonic of precocious menopause. The possibility that radiotherapy causes only a temporary alteration in ovarian activity should also be taken into consideration.

Laparoscopic gonadectomy in two patients with gonadal dysgenesis.

Individuals with androgen insensitivity syndrome have a high risk (20-30%) of developing malignancy in their gonads. Accordingly, bilateral gonadectomy is recommended. In a 17-year-old woman with Swyer syndrome gonads were located as streaks above the pelvic brim. In a 13-year-old with Morris syndrome they were located within the inguinal canals. Bilateral laparoscopic gonadectomy was performed under general anesthesia in both patients without complications. We suggest that in phenotypic females with 46,XY karyotype, the procedure may be performed safely, even with gonads located in inguinal canals.

Efficacy assessment of highly purified follicle-stimulating hormone alone or in combination with human menopausal gonadotropin during pituitary suppression in patients undergoing GIFT for unexplained infertility.

The purpose of this study was to compare the efficacy of highly purified follicle-stimulating hormone (FSH-HP) alone versus the combination of FSH-HP + human menopausal gonadotropin (hMG) treatment during pituitary suppression with gonadotropin-releasing hormone (GnRH) analog on the clinical outcome and endocrine parameters in 120 randomized women undergoing gamete intra-Fallopian transfer (GIFT) for unexplained infertility. Our data did not show any significant difference between the two groups as regards dose of administered gonadotropins, duration of treatment, estradiol 17 beta 17 beta increase curves, number of follicles > 16 mm, number of recruited and transferred oocytes, and endometrial thickness. The percentages of clinical pregnancies (33.3% with FSH-HP and 31.6% with FSH-HP + hMG), of miscarriages and twin gestations were also similar in the two groups. It is concluded that, during GnRH analog suppression, FSH-HP treatment alone is effective in inducing normal follicular steroidogenesis and adequate oocyte maturation, but no detrimental effect of luteinizing hormone (LH) activity of hMG on the outcome of the outcome of ovarian stimulation was found.

Laparoscopic conservative excision of ovarian dermoid cysts with and without an endobag.

STUDY OBJECTIVE: To compare outcomes of conservative laparoscopic treatment of dermoid cysts removed from the abdominal cavity without (group A) and with an endobag (group B). DESIGN: Prospective, randomized, 4-year (June 1992-June 1996) study (Canadian Task Force classification I). SETTING: Department of Obstetrics and Gynecology of the Catholic University of the Sacred Heart in Rome. PATIENTS: Fifty-five premenopausal women with dermoid cysts. Intervention. Patients were randomly assigned to removal of dermoid cysts from the abdominal cavity with or without an endobag through a 10- to 12-mm cannula sleeve. MEASUREMENTS AND MAIN RESULTS: We assessed surgical time, spillage, complications, length of hospitalization, recurrences, and pregnancies. In the 55 women, 58 dermoid cysts (mean diameter 5.6 +/- 2.03 cm) were enucleated and removed at operative laparoscopy through a 10- to 12-mm cannula sleeve without intraoperative or postoperative complications. Mean operating time was 73 minutes. When cysts were removed with an endobag, operating time was significantly reduced over removal without the endobag (63 vs 81 min, p <0.05). Obvious spillage of endocystic contents occurred in 13 (43.3%) patients in group A but in only 1 patient in group B because the bag ruptured (p <0.05). No signs or symptoms of peritonitis were observed in women with evident cystic spillage or in those in group A in whom spillage was possible. Average postoperative hospital stay was 1.7 days and did not differ between groups. Among 20 infertile women, 9 (45%) experienced spontaneous pregnancy within a year, with no differences between groups. Echographic follow-up did not reveal cyst recurrence. CONCLUSIONS: Laparoscopic conservative cystectomy of dermoid cysts in premenopausal women is safe and effective and appears to be a valuable alternative to laparotomy. Removing cysts in an endobag significantly reduced both operating time and spillage. However, controlled intraperitoneal spillage of cyst contents does not increase postoperative morbidity as long as the peritoneal cavity is thoroughly washed.

[Surgical treatment of ovarian cysts: economic analysis as a means for the evaluation of alternative technics. Results of a biennial study]. / Trattamento chirurgico di cisti ovariche: analisi economica come strumento di programmazione e di valutazione di tecniche. Risultati di un'indagine su un biennio.

The large use of new gynaecological technologies such as the operative laparoscopy, requires both efficacy and efficiency evaluation. The aim of this work is to compare costs of the surgical treatment of ovarian cysts between two groups of patients--35 patients undergone to laparotomic cystectomy (age: mean 27.5) and 34 operated by laparoscopic technique (age: mean 27). The analysis of the costs, related to three steps of health care (pre-operative, operative, post-operative) shows that the laparoscopic cystectomy results the more efficient intervention (L. 6,244,808 vs L. 8,310,002). This economic analysis may offer a planning tool for health care to hospital managers and represent an efficiency evaluation criterion of surgical techniques employed by the gynaecologists.

[Outcome of drug-induced pregnancies]. / Esiti di gravidanze farmacologicamente indotte.

The authors analysed 153 pregnancies achieved after different drug treatment to induce ovulation. The outcome of single and multiple pregnancies, the fetal malformation and male/female ratio were considered. The results obtained show that induction of ovulation seem to raise the risk of miscarriage when compared with outcome of spontaneous pregnancies; the malformation risk is not considerable.

Dicentric chromosome Y associated with Leydig cell agenesis and sex reversal.

The nature of a non-mosaic marker Y chromosome observed in a pseudohermaphrodite patient with Leydig cell agenesis was investigated by high-resolution chromosome analysis and molecular probes from the Y chromosome. Cytogenetically, the marker chromosome appeared to be an isodicentric, with breakage in Yq11.21. Double copies of all Yp-specific loci tested, including SRY, were present. The most distal Yq portion detected in patient DNA was DXS278-C, which maps to interval D in the chromosome Yq deletion map. Fragment DXS278-B, which maps to deletion interval E, was absent. The possible relationship between this cytogenetic abnormality and Leydig cell agenesis, a finding never reported in association with Y chromosome rearrangements, is discussed.

Utilization of long and short acting GnRH-A: effects on multiple ovulation induction for gift preparation.

The authors show the advantages of the use of GnRH-Analogues in assisted procreation: reduction of cycle cancellation; better ovulatory timing without premature luteinization; syncronous follicular recruitment with high number of mature oocytes.

[Curettage vs. hysteroscopic resection]. / Curettage v/s resezione isteroscopica.

The aim of the present study was to evaluate the therapeutic efficacy of curettage vs hysteroscopic resection in the treatment of endometrial polyps. A group of 25 patients were examined and during surgery underwent diagnostic hysteroscopy, curettage of the uterine cavity, control hysteroscopy and resectoscopy in the event of residual polyps. Thirteen cases revealed the total persistence of the polyp after curettage and in 6 cases the polyp was only partially removed; the polyp was detached but not removed from the uterine cavity in 4 cases and the polyp was fully removed using the curette in only 2 cases. The considerable limits of curettage which emerge from this study appear to be linked to three main factors: the localization, nature and size of endometrial polyps. Curettage may therefore now be considered a method which has been surpassed in not only diagnostic but also therapeutic terms by hysteroscopic techniques.

Endocrine changes and clinical outcome after laparoscopic ovarian resection in women with polycystic ovaries.

Ovarian laparoscopic resection was applied to 23 sterile patients affected with polycystic ovarian disease (PCOD) resistant to different pharmacological treatments, in order to induce ovulation. After resection, 56% of the patients had spontaneous ovulatory cycles and 13 pregnancies arose. Ten of the pregnancies were spontaneous and three followed treatment with clomiphene. Hormone changes were assessed in 15 patients, including five with spontaneous menstruation but without ovulation and five with persistent amenorrhoea for 3 months after resection. A significant decrease in both androstenedione and testosterone levels occurred in all patients. These decreases were not related to the clinical results of resection. Luteinizing hormone (LH) did not vary greatly in any group after resection. Mean values and mean pulsatility of follicle stimulating hormone (FSH) increased significantly only in pregnant patients or those with spontaneous ovulatory cycles. The results of gonadotrophin-releasing hormone (GnRH) assays did not change after resection. The mechanisms involved in the resumption of cyclic function of the hypophyseal-ovarian axis after resection are discussed briefly.

Indomethacin and fertility in experimental endometriosis.

Clinical and experimental evidence showed an increased concentration of prostaglandins in peritoneal fluid in cases of endometriosis. The aim of this study was to verify whether an antiprostaglandin drug can restore fertility in cases of endometriosis. For this reason endometriosis was induced in 4 groups of 10 rats. Group A was treated with indomethacin both in the pre-ovulatory and in the post-ovulatory phase. Group B was treated in the pre-ovulatory phase. Group C was treated in the post-ovulatory phase. Group D was not treated. Ten other rats (group E) underwent a sham operation and were used as a control. Twelve days after mating, gestational sacs and corpora lutea were counted and the nidation index was calculated. Only indomethacin administered during the pre-ovulatory phase completely restored fertility in these rats.

Efficacy of leuprorelin acetate depot in symptomatic fibromatous uteri: the Italian Multicentre Trial.

A total of 110 nonmenopausal women (mean age 42.1 years) presenting with symptomatic uterine leiomyomata and/or fibromatous uteri have been enrolled in this trial to evaluate the efficacy of the depot formulation of leuprorelin acetate in decreasing uterine volume and minimizing menorrhagia, dysmenorrhoea and pressure over the bladder. All patients were treated with an intramuscular injection of leuprorelin acetate depot 3.75 mg every 4 weeks for 16 weeks. Clinical examinations and hormonal and ultrasound determinations were performed before, during and at the end of treatment. Appropriate follow-up is still ongoing for most patients. At the end of the treatment period, of 88 women with enlarged fibromatous uteri, 33 (37.5%) showed a decrease in uterine volume of greater than or equal to 50% of the original size, while nine (10.2%) remained with unchanged uterine volume. Of 80 fibromas measurable separately, 47 (52.8%) decreased by greater than 50% of the initial volume and 16 (18%) remained unchanged or even increased. During treatment, clinically advantageous effects were observed in the associated symptomatology, mainly in the production of amenorrhoea and restoration of normal haemoglobin levels. Most of the patients were affected by irregular menstrual blood loss with consequent anaemia that in 29 patients was expressed by low levels of haemoglobin (mean 9.2 g/dl; SD 1.5; range 4.5-11.8 g/dl). By the end of the treatment, only one patient still had moderate vaginal blood loss. Haemoglobin levels rose to a mean value of 11.8 g/dl (SD 1.3; range 8.5-14.1 g/dl). Three patients (2.7%) failed to complete the 16-week treatment protocol, because of headache (one patient) and increased blood pressure (two patients). As a result of the treatment, of the 107 patients who were candidates for surgery and who were included in this study, only nine (8.4%) required surgery during leuprorelin acetate treatment. Of these, four operations were vaginal excision of the submucous myomata protruding into the cervix during treatment, and in five hysterectomy performed because of persistence of symptoms. In most patients the achievement of amenorrhoea minimized the fear of surgical emergency, facilitating an increased awareness of their clinical condition. With the exception of the three patients who dropped out, side effects were mild in all patients, consisting mainly of hot flushes, which were easily tolerated. In the following 8-12 months, the regrowth of uterine volume to original size has been usual in most of the 82 patients now in follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

The canalization of cervical mucus in the human fertility.

PIP: Canalization of cervical mucus from 31 patients at the obstetric/gynecologic clinic at the Universita Cattolica del S. Cuore in Rome, Italy has studied to determine the biochemical basis of canalization and its dependence on estrogen, to study the action on the canalization of hormones used to induce ovulation, and to correlate fern pattern and canalization. Cervical mucus was collected daily and applied to a glass slide, covered with an object cover, and allowed to dry. The typical arrangement of the dendritic crystals and the presence of channels among them were confirmed. Depending on the phase of the ovulatory cycle, the crystals differed in direction and in number. The number of channels consistently increased as estradiol levels increased during the proliferative phase. This happened in both natural and induced ovulatory cycles. The cervical mucus of patients with primary amenorrhea canalized when treated with estrogens. The channels ran parallel to each other. Yet, during the secretory phase, the number of channels fell rapidly and the channels were lined up in a crisscross fashion. This suggested that sperm penetration is dependent on the orientation of mucus crystals. Indeed in vitro studies showed that spermatozoa enter the periovulatory mucus in tightly packed files as if the mucus allowed only passage in this linear formation. The biophysical characteristics of canalization paralleled those of ferning. Moreover, like ferning, the presence of essential salts and proteins induced canalization. It is concluded that canalization can be used to accurately measure estradiol levels and thus to detect ovulation.^ieng

Current therapeutic possibilities of GIFT.

We have used GIFT in 74 couples affected with unexplained sterility, male hypofertility, endometriosis, phymosis of the fimbria and adhesions impeding oocyte pick-up. We systematically desensitized the pituitary using a GnRH analog from the 20th day of the cycle preceding GIFT. All the patients were hyperstimulated with purified FSH and hMG (Metrodin and Pergonal-Serono) from the 3rd day of the cycle. When several follicles were obtained woth a diameter greater than 16 mm together with serum estradiol values of 300 pg/ml per follicle, 10,000 IU hCG were administered intramuscularly in a single dose (Profasi-Serono). A maximum of 5 oocytes per patient were transferred (2-3 per tube). Our results confirm the validity of the GIFT method, with an average success rate of 19% in all pathological conditions and a far greater success rate in couples with unexplained sterility than in those with male hypofertility (31% and 10% respectively). The Authors stress that the best results of GIFT were achieved when the ratio between E2 and follicles with a diameter greater than 16 mm was in excess of 500 pg/ml.

GNRH therapy in hypothalamic primary amenorrhea.

Pulsatile administration of GnRH appears to be the most rational and physiological treatment of infertility in patients affected by hypothalamic amenorrhea. The authors conclude that the results obtained with this method of treatment (all patients became pregnant) suggest that the choice of pulsatile GnRH therapy is an effective and practical method for induction of ovulation.