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Biomedical subjects

R Fanchin

Publications and source records attributed to R Fanchin.

79 records · Page 5Linked to original sources

Progesterone and progestins: applications in gynecology.

Achievements obtained in infertility treatments over the past two decades have sparked interest in optimizing progesterone administration. Although progesterone is absorbed orally when ingested in micronized form, bioavailability is poor because of extensive liver metabolism. This explains why full predecidual transformation of the endometrium cannot be achieved with oral progesterone and is therefore ineffective for luteal support in in vitro fertilization (IVF). Progesterone administered non-orally can duplicate the endometrial changes normally seen in the menstrual cycle in women whose ovaries are inactive. Similar results have been reported with intramuscular (i.m.) injections and vaginal administration, although tissue levels are higher in the latter case. The recent development of a controlled and sustained release vaginal progesterone gel, Crinone(R) 8%, has made the vaginal route clinically practical by limiting the number of necessary applications to 1 per day. This regimen has been found at least as effective as intramuscular (i.m.) injections in women whose ovaries are inactive (donor egg IVF) and for luteal support in regular IVF. Hence, painful daily i.m. injections of progesterone in oil become unnecessary. The possibility of reducing the number of daily applications of vaginal progesterone to 1 per day, made possible by the sustained release gel Crinone, has opened new possibilities for long-term treatments, as in hormone replacement therapy (HRT). The low incidence of systemic side effects with use of the vaginal progesterone gel used for HRT in amenorrheic women, contrasts with findings related to use of synthetic progestins. Preliminary data suggest that vaginal progesterone can be instrumental in enhancing the notoriously poor long-term compliance of HRT.

Administration, Intravaginal↗

GnRH antagonist in single-dose applications.

Previous studies on ovarian stimulation have confirmed the efficacy of a single dose of the gonadotrophin-releasing hormone (GnRH) antagonist, Cetrorelix, in preventing premature LH surges. The single-dose protocol is easy to use and assures patient compliance. When compared with the long protocol using a depot administration of the GnRH agonist, triptorelin, the IVF results in patients treated with Cetrorelix showed a shorter treatment duration, reduced amount of human menopausal gonadotrophin (HMG) required and a lower occurrence of ovarian hyperstimulation syndrome (OHSS). The pregnancy rates did not differ significantly between the two treatments. The use of Cetrorelix in natural cycles associated with gonadotrophins reduced the rate of premature LH surges and, therefore, the cancellation rate. The stimulation was minimal and the preliminary pregnancy rates were satisfactory. If a larger study confirms the results of the natural cycle with HMG support, the single-dose administration of GnRH antagonist could represent an interesting first-choice IVF treatment in selected indications. The tolerance of Cetrorelix was excellent in all patients, with only mild and transitory reactions at the injection site. New GnRH antagonists are already available for clinical use in some countries, and they will certainly change ovarian stimulation protocols. If the pregnancy rates are confirmed, the main advantages of these new compounds are the reduction in side-effects and complications of the stimulation protocol; a clear benefit to the patients.

Drug Administration Schedule↗

Perinatal outcome and developmental studies on children born after IVF.

Since the first birth after IVF, many scientific papers have been published on the technical aspects of the IVF procedure, but few studies have addressed the issue of the perinatal outcome of IVF pregnancies and of the children's development and well-being. A high rate of adverse outcome has been demonstrated in a large group of IVF pregnancies. Prematurity, low birth weight and perinatal mortality are higher than in the general population. The majority of these complications are related to multiple births, but they are also found in singleton pregnancies. An analysis of the multiple risk factors involved in these complications is needed. The infertile status of IVF patients clearly plays a role in the risk of adverse outcome. Age and parity may be important factors. The role of IVF itself has not been demonstrated convincingly. The effect of ovarian stimulation deserves further study. Most of the studies published on the follow-up of IVF children are reassuring, but it is clear that these studies are not sufficient to eliminate without doubt any adverse effects on the well-being of IVF children. All IVF pregnancies should be followed with great care, not because they are more precious than spontaneous pregnancies, but because they are exposed to an increased risk of complications. The main problem of IVF remains the high rate of multiple pregnancies, including twins.

Age Factors↗

The use of GnRH antagonists in ovarian stimulation.

GnRH antagonists induce a rapid decrease in LH and FSH, preventing and interrupting LH surges. Their properties do not require a desensitization period, and this allows their use in the late follicular phase. GnRH antagonists could replace GnRH agonists in controlled ovarian stimulation without their side-effects and their long desensitization period. Two protocols for assisted reproduction technology (ART) cycles were designed: the single-dose protocol allies simplicity and efficacy, while the multiple-dose protocol is efficient and could reduce monitoring of the cycle, though compliance is mandatory. A review of the available literature on GnRH antagonists in ART cycles is presented, focusing on phase III controlled trials and ART results. Both protocols using GnRH antagonists were associated with the need for a smaller dose of gonadotrophin, a shorter stimulation period and a lower incidence of ovarian hyperstimulation syndrome (OHSS), albeit with statistically comparable pregnancy rates. A trend is observed in all studies showing a lower pregnancy rates in GnRH antagonist cycles as compared with GnRH agonist cycles. The role of the lower number of embryos, and the potential adverse effects of GnRH antagonists on endometrium or follicle must be studied. More cycles using GnRH antagonists are necessary to confirm their equivalent pregnancy rates. There is room for improvement in both protocols with regard to scheduling, antagonist dose level and the timing of its administration. Until further studies have been conducted, luteal support seems to remain mandatory. Perinatal outcome appears similar to that with other stimulation regimens. Triggering of ovulation can be obtained with GnRH agonist for patients at risk of OHSS. With regard to GnRH antagonists, questions remain regarding pregnancy rates, the indications of their use in patients with polycystic ovary syndrome or poor responders, and in ovarian stimulation outside IVF.

Controlled Clinical Trials as Topic↗

[Study of sperm-cervical mucus interaction in controlled cycles: feasibility of a new approach].

We report a prospective trial of in vitro sperm-mucus penetration test performed in hormonally controlled environment. To enhance the quality of the cervical mucus (CM), prevent spontaneous ovulation and to eliminate the possibility that results may be biased solely because of CM inadequacy, we conceived a 28-day physiological hormonal replacement regimen. For this women received oral estradiol valerate (E2-V) (4 mg/day) from cycle 1 to 28. CM was collected on days 13 (n = 17), 14 (n = 38) or 15 (n = 16), according to patients' individual preferences. The in vitro sperm-mucus penetration test was performed approximately 30 minutes later. On the same day, measurements of P and E2 levels were done to eliminate the possibility of spontaneous ovulation. Plasma E2 on the day of testing were 220 +/- 100 pg/ml (mean +/- SD). In all patients, except 4, P levels were low (< 1 ng/ml) on the day of the test. Our results indicate that a hormonal preparation with E2/P can be clinically useful for preventing spontaneous ovulation and reliably assuring CM quality when sperm/mucus penetration tests are performed.

Administration, Oral↗

[Uterine contractions at the time of embryo transfer: a hindrance to implantation?].

OBJECTIVES: To investigate the hormonal control and the possible consequences of uterine contractions (UC) on IVF-ET outcome. MATERIALS AND METHODS: We studied prospectively 220 controlled ovarian hyperstimulation (COH) cycles for IVF-ET. Just before ET, women underwent 5-minute digital recordings of the uterus using US image analysis software for UC assessment. Plasma progesterone (P) and estradiol were measured. Four groups were defined according to UC frequency: < or = 3.0 (n = 53), 3.1 to 4.0 (n = 50), 4.1 to 5.0 (n = 43), and > 5.0 (n = 74) UC/minute, respectively. RESULTS: Patients, COH and embryology characteristics were comparable in all groups. Notwithstanding estradiol levels were not associated with UC characteristics, plasma P and UC frequency were negatively correlated (r = -0.34, P < 0.001). A stepwise decrease in clinical and ongoing pregnancy as well as implantation rates occurred from the lowest to the highest UC frequency groups (53%, 36%, 21%; 46%, 32%, 20%; 23%, 19%, 10%; and 14%, 11%, 4%; P < 0.001). Direction of UC did not affect ET outcome. CONCLUSIONS: The negative correlation between UC frequency and P levels supports the utero-relaxing properties of P. High frequency UC on the day of ET hinder IVF-ET outcome, possibly by expelling embryos out of the uterine cavity.

Adult↗