GnRH antagonist rescue of a short-protocol IVF/ICSI cycle and GnRH agonist triggering to prevent ovarian hyperstimulation syndrome: two case reports.

OBJECTIVE: To describe two clinical cases concerning patients at risk of developing severe ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) stimulation. DESIGN: Description of clinical management and outcomes of patients using an IVF antagonist rescue protocol to prevent OHSS. SETTING: Reproductive medicine unit, University Hospital. MATERIALS AND METHODS: Two infertile patients undergoing controlled ovarian stimulation (COS) for IVF/intracytoplasmic sperm injection (ICSI) presenting with high risk of OHSS. IVF/ICSI patients following COS under short protocol and high risk of OHSS were managed by withdrawing the agonist and replacing it with an antagonist and triggering ovulation with an agonist bolus. Main outcome measures included incidence of OHSS, oocytes retrieved, and pregnancy rates. RESULTS: None of the two patients developed OHSS. None of the patients had metaphase II retrieved oocytes at oocyte retrieval. CONCLUSIONS: Use of COS with short protocol in an IVF/ICSI cycle carries a risk of severe OHSS. Rescuing the cycle by withdrawing the agonist and replacing it with an antagonist and triggering ovulation with an agonist bolus is not always effective and should not be used if short time interval between agonist replacement with antagonist and ovulation triggering is available.

Increased Maternal Serum Interleukin-6 Concentrations at 11 to 14 Weeks of Gestation in Low Risk Pregnancies Complicated with Gestational Diabetes Mellitus: Development of a Prediction Model.

The aim of the study was to examine interleukin-6 (IL-6) maternal serum concentration at 11 to 14 gestational weeks in normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Case-control study conducted in a Fetal Medicine Unit. Study population included 40 GDM cases and 94 controls. Maternal characteristics, first trimester ultrasound markers, biochemical indices, and IL-6 levels were used for our analysis. IL-6 was related to maternal weight among the maternal characteristics, (R(2)=0.0679, p=0.01). IL-6 was increased (p=0.001) in the GDM group (median=2 pg/ml) compared to the control group (median=1.5 pg/ml) even after adjustment for maternal weight. IL-6 was inversely related to birth weight adjusted for gestational age at delivery (r=-0.3382, p<0.001) and glucose levels at oral glucose test. Maternal weight and age were the only predictors of GDM among the maternal characteristics [Detection Rate (DR)=59.4%; for 25% False Positive Rate (FPR); Area Under the Curve (AUC)=0.7291; Model R(2)=0.1096, p<0.001]. IL-6 alone was a significant predictor of GDM (DR=51.3%; for 25% FPR; AUC=0.6731; Model R(2)=0.0616, p<0.001). Combination of maternal characteristics with IL-6 yielded an improved prediction (DR=67.5%; for 25% FPR; AUC=0.7586; Model R(2)=0.1521, p<0.001). IL-6 concentrations are increased at 11-14 weeks in pregnancies with GDM. Combination of maternal characteristics and maternal serum IL-6 levels may provide effective first trimester screening for GDM.

Trocar metastases in laparoscopic approach for gynecologic malignancies. A short review of the literature.

INTRODUCTION: Compared to laparotomy, laparoscopy has many benefits for patients, such as shorter recovery and lower morbidity rates. Port site metastases after laparoscopic approach in the treatment of gynecologic malignancies are uncommon. The purpose of this review is to identify and summarize possible risk factors for port-site metastases in patients undergoing laparoscopic surgery in the ambit of gynecologic oncology. DISCUSSION: The precise incidence of port-site metastases is not well known because many patients are not followed-up during the whole postoperative period. Possible risk factors that can increase the risk of port-site metastases can be the presence of large masses in the abdomen, especially in the presence of concomitant ascites and in patients treated for ovarian carcinomas. Different theories have been postulated in order to explain the development of port site metastases during laparoscopy for oncological patients. CONCLUSIONS: Patient selection is an essential factor that can influence the incidence of port site metastases in gynecological patients. Robust data regarding port site metastases in gynecologic oncology are needed.

IVF/ICSI frozen replacement cycles; every cycle? Opinion expressed after a systematic review of the literature.

OBJECTIVE: To determine whether in vitro fertilization (IVF), frozen replacement cycles offer better outcomes than fresh cycles in order to support, or not, a possible shift towards total replacement of fresh IVF/intracytoplasmic sperm injection (ICSI) cycles from frozen elective transfers (FETs). STUDY DESIGN: Systematic review; opinion paper. RESULTS: Initial results seem to support a shift in current practice towards frozen cycles. CONCLUSION: Initial results may support replacement all fresh IVF/ICSI cycles with FETs, as this could be a safer and equally effective strategy. However, robust evidence from randomized controlled trials is needed if this will be generally applied.

A rare case report of squamous-cell carcinoma arising from mature cystic teratoma of ovary.

The most frequent ovarian germ cell tumors are mature cystic teratomas (MCTs), composing 10-25% of all ovarian neoplasms. MCTs have the potential of undergoing malignant transformation, typically in postmenopausal women, with a frequency of 0.17-3%, with squamous cell carcinoma being the most common malignant tumor arising from MCT. We present the rare clinical entity of a squamous cell carcinoma arising from a mature cystic teratoma in a 56-year-old premenopausal woman as well as diagnostic and therapeutic route followed.

Effect of tibolone and raloxifene on serum markers of apoptosis in postmenopausal women.

OBJECTIVES: To investigate the effect of tibolone and raloxifene on the serum apoptotic markers soluble Fas (sFas), soluble Fas ligand (sFasL) and cytochrome-c (cyt-c) in postmenopausal women. METHODS: A total of 89 healthy postmenopausal women, attending the University Menopause Clinic, were randomly allocated to tibolone (n =30), raloxifene (n =29) or no treatment (n =30). Serum apoptotic markers sFas, sFasL and cyt-c were measured at baseline and at 6 months. RESULTS: Serum sFasL decreased significantly in women receiving tibolone (baseline: 53.8±28.3 pg/ml, 6 months: 40.45±19.2 pg/ml, p =0.001), whilst sFas levels did not significantly change in this group. Serum sFas or sFasL did not change either in the raloxifene group or in the control group. Serum cyt-c concentrations were under the detection limit of the assay in all women assessed. CONCLUSIONS: Tibolone use resulted in a significant decrease in serum sFasL, but not in serum sFas. Raloxifene had no effect on either sFas or sFasL. These results may indicate that tibolone use is associated with a decrease in receptor-mediated apoptosis.

Does hormone therapy, tibolone or raloxifene modify VEGF expression in cervical epithelial cells?

AIM: Vascular endothelial growth factor (VEGF) seems to be a critical molecule in cervical carcinogenesis. We aimed to investigate the possible associations between hormonal factors and VEGF expression in cervical epithelial cells from postmenopausal women. METHOD: A total of 105 healthy postmenopausal women (aged 45-68 years old) attending a university menopause clinic were enrolled in this cross-sectional study. Pap smears were derived from current users of 17ß-estradiol 1 mg + norethisterone acetate 0.5 mg (n = 28), tibolone 2.5 mg (n = 23), raloxifene HCl 60 mg (n = 21) and women not receiving treatment (n = 33). VEGF immunostaining was evaluated in squamous, glandular and metaplastic cells, using a semiquantitative method (rating scale: 0-3). RESULTS: Concerning endogenous hormones, higher Δ4-androstenedione levels were associated with more intense VEGF immunostaining in glandular (p = 0.041) and metaplastic cells (p = 0.004). Hormone therapy and raloxifene did not induce any changes in VEGF immunoreactivity in the examined cells. In contrast, tibolone administration was accompanied by diminished VEGF presence in metaplastic cells (p = 0.016 vs. controls). CONCLUSION: Our findings may in part reflect the molecular processes contributing to the safe profile of hormone therapy, tibolone and raloxifene in cervical carcinogenesis.

Human papilloma virus molecular profile and mechanisms of cancerogenesis: a review.

Human papilloma virus (HPV) is frequently present in the genital tract. It causes various lesions at the mucosa of both sexes. It is considered as a causative factor of cervical cancer even if all women infected by HPV will not develop the disease. This article reviews aspects of HPV molecular biology and the mechanisms of cancerogenesis in HPV infected females.

Progestin may modify the effect of low-dose hormone therapy on mammographic breast density.

OBJECTIVES: To evaluate the effect on breast density of two low-dose hormone therapy regimens identical in their estrogen component but different in the progestin. METHODS: A total of 81 non-hysterectomized postmenopausal women were allocated either to 17beta-estradiol 1 mg and norethisterone acetate 0.5 mg (E2/NETA, n = 43) or to 17beta-estradiol 1 mg and drospirenone 2 mg (E2/DRSP, n = 38). Treatment was continuous and lasted 12 months. The main outcomes were the changes in breast density according to the Wolfe classification between baseline and 12-month mammograms. RESULTS: Involution of the fibroglandular tissue was not seen in either of the treatment groups. Under E2/NETA, breast density increased in seven women (16.3%). In contrast, only three women (7.9%) exhibited a density increase under E2/DRSP. CONCLUSIONS: Although hormone therapy appears to suspend breast involution, it does not increase breast density in the majority of treated women. Progestins differing in pharmacological properties may have a variable impact on breast density.

Ultrasound imaging to evaluate Creatsas vaginoplasty.

OBJECTIVE: To present a new imaging technique for the evaluation of the functional effectiveness of Creatsas vaginoplasty. METHOD: Eighteen women with Mayer-Rokitansky-Kuster-Hauser syndrome underwent a transabdominal and transperineal ultrasound examination 4 weeks and 6 months after the surgical creation of a neovagina, and then yearly, with a condom filled with water as a distending and imaging medium. The functional length and width of the neovagina and its axis deviation were assessed, as well as the postoperative quality of the women's sexual life. RESULTS: A functional vagina 10 to 12 cm in length and 4 to 5 cm in width was observed; its axis deviation, which was similar to the anatomic deviation, was easily determined; and 94.5% of the women reported a satisfactory while 5.5% reported an adequate sexual life. CONCLUSION: This new imaging technique is a simple and effective alternative for the evaluation of the postoperative effectiveness of colpopoiesis.

Prediction of preterm delivery by sonographic estimation of cervical length.

BACKGROUND: Identification of pregnant women presenting with threatened preterm labor who are destined to deliver prematurely would greatly assist planning their management. OBJECTIVES: The purpose of the study was to evaluate the ultrasonographic measurement of cervical length as a prognostic factor for predicting preterm birth in cases of threatened preterm labor. METHODS: The study included 104 women with singleton pregnancies who presented with threatened preterm labor at 24-36 weeks of gestation. Cervical length at presentation was evaluated by transvaginal ultrasonography. Other potential prognostic factors, such as previous history of preterm labor, smoking, parity and administration of tocolytics were assessed. All women were observed for preterm delivery within 7 days of presentation. RESULTS: The only significant predictor of preterm delivery was cervical length assessed by ultrasound (p<0.000001, odds ratio 93.3, 95% Cl 10.4-837.1). CONCLUSIONS: Cervical length assessed by transvaginal ultrasonography in women presenting with threatened preterm labor is a powerful predictive tool for progression to preterm delivery.

The effect of compounds altering the cAMP level on reversing the 2-cell block induced by hypoxanthine in mouse embryos in vitro.

The possibility of reversing the hypoxanthine induced 2-cell block in mouse embryos when cultured in conditions supplemented with compounds that increase (FSH, hMG, IBMX, hCG) or inhibit (GnRH-analogue) cAMP was assessed. When embryos were cultured in Ham's F-10 without hypoxanthine supplemented with each of the above compounds, no inhibition of blastocyst development was observed. Embryos were then cultured in Ham's F-10 with hypoxanthine supplemented again with each compound. For the addition of GnRH-analogue or FSH, the rate of blastocyst formation was comparable with that of the control medium with hypoxanthine alone. Instead, the addition of IBMX or hMG reversed the induced block. There was no reversible effect for the addition of 2 micrograms/ml hCG while the latter was observed with higher doses. The results from GnRH-analogue and IBMX addition show that, contrary to what was found for oocytes, stimulation of cAMP reverses the hypoxanthine-induced block in mouse embryos. FSH and hCG also had effects opposite to those observed for oocytes. It is unknown why hMG (FSH + LH) reverses the block. A lower cAMP degradation rate resulting in a higher cAMP level is a possible explanation. Our results provide further evidence that cleavage arrest by hypoxanthine has a different mechanism than the hypoxanthine-induced arrest of meiosis.

Preovulatory effects of the progesterone antagonist mifepristone (RU486) in mice.

The progesterone antagonist mifepristone (RU486), was given in mice once on different days of pregnant mare's serum gonadotrophin-human chorionic gonadotrophin (PMSG-HCG) treatment and its action upon the induction of ovulation studied. RU486 administered on the day after PMSG significantly reduced the ovulation rate. Ovulation was completely inhibited when the progesterone antagonist was given simultaneously with HCG, but RU486 administered 4 h after HCG treatment remained ineffective. The development of two-cell zygotes harvested on day 2 post-coitum from mice treated with RU486 on the day after the PMSG treatment was followed in vitro and showed a significant decrease in the number of embryos developing to blastocysts. These results favour the involvement of progesterone in the ovulation process, indicating a direct effect of this hormone at the ovarian level via a progesterone receptor-mediated action.