George Pados

GnRH-agonist versus GnRH-antagonist IVF cycles: is the reproductive outcome affected by the incidence of progesterone elevation on the day of HCG triggering? A randomized prospective study

BACKGROUND In view of the current debate concerning possible differences in efficacy between the two GnRH analogues used in IVF stimulated cycles, the current study aimed to explore whether progesterone control in the late follicular phase differs when GnRH antagonist is used as compared with GnRH agonist, and if so, to what extent the progesterone rise affects the probability of pregnancy. METHODS Overall 190 patients were randomized: 94 in the GnRH-agonist group and 96 in the GnRH-antagonist group. The GnRH-agonist long protocol started on Day 21 of the preceding cycle with intranasal buserelin (600 mg per day). The GnRH-antagonist protocol started on Day 6 of the stimulation with ganirelix or cetrorelix (each 0.25 mg). All blood samples were analysed with the Elecsys analyzer. An intention-to-treat analysis was applied. RESULTS A progesterone rise >1.5 ng/ml was noticed in 23.0% of the antagonist group, comparable with 24.1% incidence within the agonist group. Per patient randomized, delivery rates were also comparable: 28.1% in the antagonist group and 24.5% in the agonist group (odds ratio = 1.21, 95% confidence interval: 0.63-2.31, P= 0.56). However, there was a reduction in delivery rates when progesterone exceeded the threshold of 1.5 ng/ml, both in the agonist group (9.5 versus 31.8%, P= 0.03) and in the antagonist group (14.3 versus 34.3%, P= 0.07). CONCLUSIONS Although the incidence of a progesterone rise was similar between the two analogues, our findings reconfirm previous observations that insufficient progesterone control (>1.5 ng/ml) on the day of ovulation triggering is related to poor delivery rates in both protocols. The current study has shown that the reproductive outcomes with the two GnRH analogues are comparable. Possible modes of action to circumvent late follicular progesterone rise should be explored. TRIAL REGISTRATION NUMBER NCT01191710.

Prevention of intra-peritoneal adhesions in gynaecological surgery: theory and evidence

Post-operative adhesions are a significant complication of all abdominal surgical procedures. The major strategies for adhesion prevention in gynaecological surgery are focused on the optimization of surgical technique and use of anti-adhesive agents, which fall into two main categories: pharmacological agents and barriers. Surgical technique that minimizes peritoneal trauma can reduce, but cannot prevent post-operative adhesion formation. Various local and systemic drugs that can alter the local inflammatory response, inhibit the coagulation cascade and promote fibrinolysis have been evaluated. Limited data support the administration of post-operative corticosteroids in addition to systemic intra-operative corticosteroids for the prevention of adhesions after gynaecological surgery. None of the remaining pharmacological agents have been found effective for the reduction of post-operative adhesions. Barriers are currently considered the most useful adjuncts, which may reduce adhesion formation. They act by separating the traumatized peritoneal surfaces during the healing period. The separation can be achieved by solid barriers or fluids. There is limited evidence from randomized clinical trials that support the beneficial effect of most of these barrier agents in the prevention of intra-peritoneal adhesions after gynaecological surgery. However, the evidence is not adequate for definite conclusions to be drawn and further research in this field is warranted.

Aromatase inhibitors in stimulated IVF cycles

Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels

Laparoscopic Management of the Adnexal Mass

Abstract:  In the past few years the contribution of operative laparoscopy in all fields of gynecological surgery has been revolutionary. Nowadays laparoscopic management of adnexal masses is the most frequently performed laparoscopic intervention. Laparoscopy in comparison to laparotomy has the advantages of lower morbidity, shorter length of hospital stay, decreased postoperative pain, lesser de novo adhesion formation, better cosmetic results, faster recovery, and reduced overall cost of care. However, careful preoperative evaluation is important for the appropriate and successful use of laparoscopy for removal of adnexal masses and the advantages of the laparoscopic approach should, in no way, compromise the clinical outcome in women with malignancy. Patients age, history, findings of physical examination, and the results of serum markers in combination with the imaging assessment, such as Doppler sonograpy, CT, or MRI, should be considered to reach the diagnosis preoperatively. However, only pathology of the adnexal mass can provide the definitive diagnosis. The specific characteristics of the adnexal masses in childhood, adolescent, reproductive, and postmenopausal age represent the essential parameters that will determine the therapeutic strategy to be followed. Furthermore, the clinician has to determine whether an adnexal mass requires surgery or expectant management as well as to estimate the possibility of malignancy.

Ultrasound and MR-imaging in preoperative evaluation of two rare cases of scar endometriosis

Scar or incisional endometriosis is a rare, often misdiagnosed, pathologic condition of the abdominal wall. Two cases of incisional endometriosis are presented. Both patients presented with atypical cyclic pain and palpable nodules on scars of previous cesarean sections. In both cases, the mass was totally excised, after accurate preoperative evaluation with 2-D ultrasound, power Doppler and MRI. Microscopic examination confirmed the preoperatively presumed diagnosis of cutaneous endometriosis. In cases of suspected scar endometriosis, preoperative diagnostic imaging is valuable in determining the extent of disease, thus enhancing accurate and total excision.

Oocyte donation: clinical and practical aspects

Oocyte donation is an effective treatment modality for women lacking functioning ovaries, but also for women in whom repetitive in-vitro fertilization (IVF) cycles did not result in the development of adequate number of oocytes as well as for those at risk of transmitting genetic diseases. In women with ovarian failure, artificial menstrual cycles are required in order to produce endometrial growth and differentiation similar to that in women with normal ovarian function. Synchronization of donors and recipients cycles is mandatory, since the window of implantation is rather limited. The excellent results of oocyte donation treatment confirm that this assisted reproduction technique can provide a novel approach for the treatment of infertility in these groups of patients. Nevertheless, pregnancies in women of advanced reproductive age are associated with significantly more obstetrical complications and higher perinatal morbidity and mortality rates. Furthermore, aging parents have considerably higher chances to develop serious or life-threatening diseases. Thus, careful medical screening and extensive counselling is mandatory, taking into account the psychosocial ramifications of the procedure and, especially, the best interest of the child-to-be.

Reproductive and obstetric outcome after laparoscopic excision of functional, non-communicating broadly attached rudimentary horn: a case series.

OBJECTIVE To present the reproductive and obstetric outcome after laparoscopic excision of functional, non-communicating broadly attached rudimentary horn. STUDY DESIGN As a part of a retrospective study performed over the past 21 years to determine the reproductive and obstetric outcome after laparoscopic treatment for symptomatic non-communicating rudimentary horn, we identified seven women who became pregnant after laparoscopic removal of the broadly attached rudimentary horn. The main outcome measures were reproductive outcome, preterm birth, mode of delivery, birth weight, pregnancy-induced hypertension, antenatal bleeding and presence of other congenital anomalies. RESULTS Infertility was present in 3 out of 8 cases (37.5%), although in 2 of them other confounding infertility factors existed. Seven out of 8 patients conceived, 2 of them by assisted reproduction techniques. All patients had a preterm delivery at 33 weeks of gestation (32.5±2.4) by cesarean section due to pregnancy-induced hypertension (3 cases), IUGR (one case), contractions and hemorrhage (one case), while two were elective. The mean weight of infants was 1897±607.8 g. Pregnancy-induced hypertension was observed in 3 and antenatal vaginal bleeding occurred in 5 patients. All infants are alive with no apparent congenital anomaly. CONCLUSIONS This case series confirms that pregnancies in women after laparoscopic excision of broadly attached rudimentary horns should be considered as high-risk ones and should be managed accordingly to ensure a satisfactory obstetric outcome.

Prenatal management and postnatal separation of omphalopagus and craniopagus conjoined twins

Two cases of prenatally diagnosed conjoined twins are presented: a set of omphalopagus twins sharing a common liver, and a set of craniopagus with involvement limited to the skull. In both cases, prenatal diagnosis allowed accurate planning of pre- and postnatal management. Prenatal management involved serial imaging and counseling with participation of different specialists according to imaging findings. In the rare case of conjoined twins, an interdisciplinary approach is required, with feto-maternal specialists playing a pivotal role in co-ordinating teamwork and planning successive stages of management.

Adhesion Prevention Strategies in Laparoscopic Surgery

Adhesions are defined as abnormal attachments between tissues and organs [1]. Intra-ab‐ dominal adhesions may be classified as congenital or acquired [2]. Congenital adhesions are a consequence of embryological anomaly in the development of the peritoneal cavity. Ac‐ quired adhesions result from the inflammatory response of the peritoneum that arises after intra-abdominal inflammatory processes (e.g. acute appendicitis, pelvic inflammatory dis‐ ease, exposure to intestinal contents and previous use of intrauterine contraceptive devices), radiation and surgical trauma [3]. It has been reported that the majority of acquired adhe‐ sions (about 90%) are post-surgical [2].

Evaluation of different ovarian stimulation protocols for in vitro fertilization

In this study we evaluated retrospectively the efficacy of five different ovarian stimulation protocols in an in vitro fertilization program, in which 512 women were involved. Ovulation was induced by the following protocols: group I (271 cycles): buserelin short protocol (1 mg/day, intranasally) with human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG); group II (45 cycles): buserelin (short protocol) with pure follicle stimulating hormone (p-FSH)/hMG/hCG; group III (24 cycles): clomiphene citrate (100 mg/day) with hMG/hCG; group IV (122 cycles): hMG (3 ampules/day) and hCG; group V (113 cycles): hMG/hCG and prednisolone (7.5 mg/day) after cycle programming with oral contraceptives. The lowest cancellation rate (3.3%) was noted in group I, followed by group V (9.7%). The highest number of follicles was observed in groups I (8.3 +/- 0.3; mean +/- SEM) and V (7.8 +/- 0.5). Also, more oocytes were retrieved in group I (7.2 +/- 0.3, p < 0.001), which were of good quality based on oocyte maturity as well as on the fertilization rate, and more embryos (4.5 +/- 0.3, p < 0.05) were developed. The correlation between estradiol and the total follicular volume on the day of hCG administration was also examined in the five groups. The best correlation (r = 0.6502) was found in group I, followed by group V (r = 0.5810). Significant differences were observed in the five groups with regard to the number of hMG ampules administered (p < 0.0001, F = 15.393) and the stimulation days (p < 0.0001, F = 35.32). Sixty-six clinical pregnancies were achieved: 37 (17.5%) in group I, seven (25.9%) in group II, one (10%) in group III, ten (15.6%) in group IV and 11 (15.5%) in group V (differences were not statistically significant). In conclusion, all five protocols were satisfactory in ovarian stimulation for in vitro fertilization, and gonadotropin releasing hormone (GnRH) analogs seemed to be more advantageous by reducing the cancellation rate, enhancing the number of oocytes retrieved and embryos developed and by improving the pregnancy rates.