Stefano Venturoli

Clinical experience and applications of oocyte cryopreservation

Oocyte cryopreservation is a viable solution for the ethical problems related to embryo storage, and the only available technique for preservation of fertility in women who have to undergo chemo- or radiotherapy. The main problems with oocyte cryopreservation are concerned with the survival rate and the fertilization rate. Recently the introduction of the intracytoplasmic sperm injection (ICSI) led to an increase in the fertilization rate. The success achieved with the first case treated encouraged us to set up a clinical trial on human oocyte cryopreservation. In the first stage of the study, 23 women with tubal infertility were enrolled. Superovulation was induced and 375 oocytes were retrieved; of these 338 oocytes were frozen. The survival rate was 59.5% and was independant of the duration of cryopreservation or the presence of cumulus. The normal fertilization rate was 64.4%, and only 7.5% of fertilizations were abnormal. A total of 90.8% of fertilized oocytes cleaved. A mean of 3.1+/-1.3 embryos per patient were transferred. Three pregnancies were achieved. In the second stage of our investigation, more patients were enrolled and similar results were observed. Sixteen pregnancies were achieved. A further stage of the investigation involved the fertilization of frozen oocytes with frozen sperm and even these resulted in a pregnancy. Our study demonstrated that pregnancies can also be achieved when frozen eggs are fertilized by testicular and epididymal sperm. As a consequence of the success of our investigations, a program of oocyte cryopreservation for oncological patients has been initiated in our centre. In our opinion, oocyte cryopreservation is, at present, a safe and efficient technique as documented by the birth of several healthy children.

Long-term cyclic and continuous oral contraceptive therapy and endometrioma recurrence: a randomized controlled trial

OBJECTIVE To evaluate long-term cyclic and continuous administration of oral contraceptive pills (OCP) in preventing ovarian endometrioma recurrence after laparoscopic cystectomy. DESIGN Prospective, randomized, controlled trial. SETTING Tertiary care University Hospital. PATIENT(S) Two hundred thirty-nine women who underwent laparoscopic excision of ovarian endometriomas. INTERVENTION(S) Patients were divided randomly into three groups: nonusers receiving no therapy and cyclic and continuous users receiving low-dose, monophasic OCP for 24 months in cyclic or continuous administration, respectively. MAIN OUTCOME MEASURE(S) Endometrioma recurrence, size of recurrent endometrioma, and growth rate during at least 2 years follow-up evaluated by transvaginal ultrasonography. RESULT(S) The crude recurrence rate within 24 months was significantly lower in cyclic (14.7%) and continuous users (8.2%) compared with nonusers (29%). The recurrence-free survival was significantly lower in nonusers compared with cyclic and continuous users. The mean recurrent endometrioma diameter at first observation was significantly lower in cyclic (2.17 +/- 0.45 cm) and continuous users (1.71 +/- 0.19 cm) compared with nonusers (2.73 +/- 0.56 cm). The mean diameter increase every 6 months of follow-up was significantly reduced in cyclic users (0.31 +/- 0.18 cm) and continuous users (0.25 +/- 0.09 cm) versus nonusers (0.48 +/- 0.3 cm). No significant differences between cyclic users and continuous users in terms of endometrioma recurrence were demonstrated. CONCLUSION(S) Long-term cyclic and continuous postoperative use of OCP can effectively reduce and delay endometrioma recurrence.

Body fat distribution has weight-independent effects on clinical, hormonal, and metabolic features of women with polycystic ovary syndrome

This study was performed to investigate whether different patterns of body fat distribution may have distinct effects on the clinical, hormonal, and metabolic features of women with clinical hyperandrogenism such as polycystic ovary syndrome (PCOS). Ninety-seven consecutive women with PCOS were included in the study after assessment of gynecological and obesity history and careful clinical examination. Women were divided into three tertile groups based on the waist to hip ratio (WHR). Those with peripheral body fat distribution (P-BFD) had a WHR of less than 0.80, those with intermediate body fat distribution (I-BFD) had a WHR of 0.81 to 0.90, and those with abdominal body fat distribution (A-BFD) had a WHR exceeding 0.90. Baseline blood and urine samples were obtained for several hormone and lipid determinations, and the response of glucose, insulin, and C-peptide to a glucose oral challenge (75 g) was investigated. In the PCOS group, WHR values were higher than those used to define P-BFD and A-BFD in the normal female population. As WHR values increased, a significantly greater prevalence of obesity and acanthosis nigricans and a lower prevalence of acne was present. No significant differences were present in any of the other clinical features between the three groups. Ovarian morphology and volumes were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term oral contraceptive pills and postoperative pain management after laparoscopic excision of ovarian endometrioma: a randomized controlled trial.

OBJECTIVE To evaluate postoperative long-term cyclic and continuous administration of combined oral contraceptive (OC) pills in preventing endometriosis-related pain recurrence. DESIGN Prospective, randomized, controlled trial. SETTING Tertiary care university hospital. PATIENT(S) Three hundred eleven women who underwent laparoscopic excision for symptomatic ovarian endometrioma. INTERVENTION(S) Patients were randomly divided into three groups: nonuser group receiving no therapy, and cyclic user group and continuous user group receiving low-dose, monophasic OC pills for 24 months in either cyclic or continuous administration. MAIN OUTCOME MEASURE(S) Presence and intensity of dysmenorrhea, dyspareunia, and chronic pelvic pain were assessed by a 10-point visual analogue scale (VAS) at 6, 12, 18, and 24 months postoperatively. RESULT(S) A significant reduction in recurrence rate and VAS scores for dysmenorrhea was evident in the continuous users versus the other groups at 6 months, and in cyclic users versus nonusers at 18 months postoperatively. No significant differences in recurrence rate and VAS scores for dyspareunia and chronic pelvic pain were demonstrated among the groups. The increase of VAS scores from 6-24 months during the study period for dysmenorrhea, dyspareunia, and chronic pelvic pain was significantly higher in nonusers than in the other groups. CONCLUSION(S) Long-term postoperative use of OC pills can reduce the frequency and the severity of recurrent endometriosis-related dysmenorrhea.

Ultrasonic findings in polycystic ovarian disease

The uterus and ovaries of 50 patients with polycystic ovarian disease (PCOD) and 30 eumenorrheic women were studied with a real-time ultrasound mechanical sector scanner. Uterine and ovarian volumes (UV and OV) and the OV/UV ratio were calculated, and ovarian morphology was classified as prevalently solid and cystic. Both ovaries were displayed in 44 of the PCOD and in 25 of the normal patients and appeared bilaterally solid, cystic, or with different morphology, respectively, in 43.2%, 47.7%, and 9.1% of cases in the former group and in 76%, 20%, and 4% in the latter group. Statistically significant differences between normal and PCOD patients were found in OV, UV, and OV/UV ratio. Bilaterally enlarged ovaries with multiple tiny cysts, the classic ultrasonographic picture of the polycystic ovary, were found in only 16 (36.3%) of the PCOD cases, while 34 (77.3%) had an OV/UV ratio greater than 1 standard deviation above the mean. Four ultrasonographic ovarian patterns were observed in the PCOD patients: enlarged cystic; enlarged solid; normal-sized cystic; and normal-sized solid. These findings emphasize the need for a reconsideration of the ultrasonographic criteria of PCOD.

Surgical outcome and long-term follow up after laparoscopic rectosigmoid resection in women with deep infiltrating endometriosis

The aim of this study was to assess the long‐term outcome of treating severely symptomatic women with deep infiltrating intestinal endometriosis by laparoscopic segmental rectosigmoid resection. Detailed intraoperative and postoperative records and questionnaires (preoperatively, 1 month postoperatively and every 6 months for 3 years) were collected from 22 women. The estimated blood loss during surgery was 290 ± 162 ml (range 180–600), and average hospital stay was 8 days (range 6–19). One woman required blood transfusion after surgery. Two cases were converted to laparotomy. One woman had early dehiscence of the anastomosis. Six months after surgery, there was a significant reduction of symptom scores (greater than 50% for most types of pain) related to intestinal localisation of endometriosis (P < 0.05). Score improvements were maintained during the whole period of follow up. Noncyclic pelvic pain scores showed significant reductions (P < 0.05) after 6 and 12 months, but there was a high recurrence rate later. Dysmenorrhoea and dyspareunia improved in 18/21 and 14/18 women with preoperative symptoms, respectively. Constipation, diarrhoea and rectal bleeding improved in all affected women for the whole period of follow up. Laparoscopic segmental rectosigmoid resection seems safe and effective in women with deep infiltrating colorectal endometriosis resulting in significant reductions in painful and dysfunctional symptoms associated with deep bowel involvement.

Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom-recurrence after conservative surgery for endometriosis

BACKGROUND Endometriosis recurrence after conservative surgery is not infrequent. Variable regimens of hormonal therapy have been proposed as adjuvant post-operative measures for prophylaxis against recurrence. Among these, the combined oral contraceptive pills (OCP), represents a valuable option in terms of safety and tolerability for long-term use. The objective of this review is to evaluate the effect of post-operative use of OCP in preventing symptom recurrence, and/or anatomical relapse of endometriosis. METHODS A systematic search of Medline identified seven studies evaluating post-operative OCP treatment on prevention of endometriosis recurrence. RESULTS A reduction in anatomical relapse rate was observed when oral contraceptive therapy was administered for more than 1 year after conservative surgery. Post-operative use of OCP was associated with a reduction in frequency and intensity of dysmenorrhoea recurrence. No association was found between OCP therapy and dyspareunia prevention, although the effect of OCP on chronic pelvic pain was conflicting. CONCLUSION Long-term OCP therapy can be a reliable adjuvant post-operative measure to prevent or reduce frequency/severity of recurrent dysmenorrhoea and anatomical relapse of endometriosis. Since both continuous and cyclic OCP administration regimens seem to have comparable effects, the choice of regimen can be modulated according to patient preferences. The protective effect seems to be related to the duration of treatment.

Longitudinal Change of Sonographic Ovarian Aspects and Endocrine Parameters in Irregular Cycles of Adolescence

ABSTRACT: We longitudinally studied clinical endocrine and ultrasound parameters of the ovaries in 73 healthy adolescents having persistent menstrual irregularities. After the first examination, they were reexamined after a variable period ranging from 2 to 7 y. During the first examination, three basic features of the ovaries were observed: homogeneous (36%), multifollicular (23%), and polycystic (41%). Polycystic ovaries were most frequent, and they generally exceeded the normal adult range. During the last examination, in the entire group of irregular adolescents, homogeneous ovaries decreased (–14%), polycystic ovaries increased (+ 18%), and a further higher number of subjects exceeded the normal adult range (+10%). The subjects with enlarged ovaries had the highest values of LH, testosterone, and androstenedione. Fourteen subjects out of 46 (30%), with normal ovarian volume in the first examination, registered an ovarian enlargement in the last examination, exceeding the normal range. Moreover, a change from the homogeneous or multifollicular structure to the polycystic one was observed. Twenty-one subjects out of 27 (78%) with enlarged ovaries in the first examination confirmed the high ovarian volume and the unchanged structure in the last examination, whereas six subjects (22%) showed ovaries within the normal adult range; the polycystic structure was substantially confirmed. These results indicate the following. 1) Homogeneous, multifollicular, and polycystic ovaries can usually be found in the postmenarcheal period. 2) Enlarged ovaries, polycystic structure, hyperandrogenemia, and high LH values are strongly linked, and they are frequent in irregular cycles even in the absence of signs of hyperandrogenism. These characteristics may all persist or in various aggregations become a permanent feature. 3) Only a few subjects may lose ovarian enlargement and show a change in the polycystic structure; however, they frequently maintain hyperandrogenemia. 4) During the postmenarcheal period, normal ovarian characteristics may suddenly change, and the ovaries may take on a polycystic structure and increase in volume. Moreover, some endocrine parameters may reach pathologic levels.

Fertility and tumor recurrence rate after conservative laparoscopic management of young women with early-stage borderline ovarian tumors

OBJECTIVE To evaluate the efficacy of laparoscopic conservative surgery in young women with borderline ovarian tumors who want to preserve their childbearing potential, and to assess whether pregnancy influences the recurrence rate during the follow-up evaluation period. DESIGN Retrospective study. SETTING Center for Reconstructive Pelvic Endosurgery, Reproductive Medicine Unit, S. Orsola Hospital, University of Bologna, Italy. PATIENT(S) Nineteen women (mean age 27.4 +/- 4.7) with borderline ovarian tumors who underwent laparoscopy between January 1995 and January 1998. All of the women wanted to preserve their fertility. INTERVENTION(S) A standardized conservative laparoscopic approach and a strict follow-up schedule. MAIN OUTCOME MEASURE(S) A complete preoperative examination. RESULT(S) Follow-up evaluations (mean 42 +/- 19 months) were made available to all patients. Among 19 patients, 10 attempted pregnancy and 6 conceived spontaneously. All six pregnancies went to term and the disease did not affect the gestation or the follow-up period after the pregnancy (24.5 +/- 15.7 months). CONCLUSION(S) Conservative laparoscopic management of borderline ovarian tumors is a potentially safe alternative in young women who want to retain their childbearing potential. Fertility and pregnancy outcome remain excellent in these women. Our preliminary data seem to indicate that the recurrence rate after pregnancy is not influenced by this approach.

Meiotic spindle recovery is faster in vitrification of human oocytes compared to slow freezing

OBJECTIVE To investigate spindle behavior during and after slow freezing at room temperature (RT) and vitrification at different temperatures. DESIGN Randomized, comparative study. SETTING University hospital. PATIENT(S) Patients undergoing IVF treatment volunteered for the study and donated part of their supernumerary oocytes. INTERVENTION(S) Metaphase II oocytes were divided into group A: slow freezing RT /thawing RT; group B: vitrification RT/warming RT; group C: vitrification RT/warming 37 degrees C; and group D: vitrification 37 degrees C/warming 37 degrees C. Spindle presence was evaluated at each step of the four procedures and in culture. MAIN OUTCOME MEASURE(S) Cumulative spindle recovery rate comparing warming phase of the three vitrification groups and culture phase among the four groups. RESULT(S) During warming, the three vitrification groups showed a significantly fast spindle recovery rate compared to the thawing of the slow freezing group. A progressively significant fast cumulative recovery rate was observed in the three vitrification groups by increasing the number of phases at physiological temperature (hazard rate = 2.68; 95% confidence interval 1.71-4.02). CONCLUSION(S) The present study demonstrates that spindle recovery is faster in vitrification than in slow freezing. These data support a possible protective effect of vitrification/warming at 37 degrees C on the meiotic spindle structure and, therefore, on the subsequent clinical outcome of the procedure, although comparative clinical studies are needed.