Effect of simultaneously started clomiphene citrate and gonadotropins in antagonist regimes, on cumulative live births, fresh-cycle live births and cost of stimulation in IVF cycles.

AIM: The aim of the study was to compare simultaneously started clomiphene citrate (CC) and gonadotropins (Gn) with gonadotropins alone in conventional antagonist regimes with respect to fresh-cycle live births, cumulative live births and cost of ovarian stimulation per started cycle. METHODS: This was a single-center prospective cohort study conducted over 1 year. Women undergoing autologous in vitro fertilization (IVF) treatment in antagonist protocols and who consented to participate in the study were divided into two cohorts. The CC cohort (n = 86) received 50 mg CC for 5 days and individualized Gn daily until the hCG trigger, both starting from day 2 and antagonist daily from day 8 of menstrual cycle. The Gn-only cohort (n = 349) received individualized Gn from day 2 and the antagonist from day 7 of menstrual cycle. IVF outcomes and cost of stimulation were compared between two cohorts across expected ovarian response categories. RESULTS: The CC cohort used a mean lower dose of Gn (1741.38 ± 604.46 vs 1980.54 ± 686.42; MD = -239.16; 95%CI = -348.03 to -189.24; P = 0.003) over fewer days (8.54 ± 1.86 vs 9.25 ± 1.97; MD =-0.71;95% CI = -1.17 to -0.25; P = 0.0026) to achieve similar retrieved oocytes, (9.19 ± 5.92 vs 9.36 ± 6.96; MD = -0.17; 95%CI -1.77 to + 1.43; P = 0.83), positive bhCG rates (40% vs 29.6%, MD = 10.4%; OR = 1.65, 95%CI = 0.95-2.86; P = 0.078) and live births in fresh cycles (32.31% vs 21.30%; MD = 11.01%; OR = 1.76; 95%CI = 0.97-3.19; P = 0.06) and cumulative live births per initiated cycle (30.23% vs 20.34%; MD = 9.89%; OR = 1.697; 95%CI = 0.99-2.88; P = 0.0501). The dose lowering achieved a 28-40% reduction in the cost of stimulation, which was most noticeable in the hyper-responder category for both hMG cycles, (Rs.11 602.3 ± 3365.9 vs 19615 ± 2677.1; MD = -8012.7; %age reduction: 40.8%; P = 0.0007) and recombinant FSH cycles (Rs. 22 459.6 ± 6255.3 vs 33 022.1 ± 9891.2; MD: -10 562; %age reduction: -32%; P = 0.0001). CONCLUSION: CC started simultaneously with Gn in antagonist regimes helps lower the cost of stimulation without affecting IVF outcomes.

Quality assessment of induced spermatogenesis in hypogonadotrophic hypogonadic men treated with gonadotrophins.

Hypogonadotrophic hypogonadism (HH) is characterized by deficient gonadotrophin secretion, resulting from pituitary or hypothalamic defects. In order to induce spermatogenesis, HH patients are treated with commercially available gonadotrophins. As far as is known, quality and genetic integrity of induced sperm cells have never been investigated, although they represent an important issue, since the ultimate goal of this treatment is to have competent spermatozoa in order to achieve paternity. In order to evaluate the nuclear integrity of induced sperm cells, sperm samples from treated HH patients were compared with sperm samples from normospermic control donors. Sperm cells were analysed by fluorescence in-situ hybridization, using probes specific for chromosomes 13, 21, 18, X and Y, and by TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay. Results showed that the rate of aneuploid and diploid sperm cells in patients was not statistically different from controls and that the rate of sperm cells with fragmented DNA was within the normal values. Spermatozoa obtained by gonadotrophin treatment in HH patients are likely to have a balanced chromosomal content and a normal DNA integrity but this conclusion needs to be confirmed by further studies dealing with a greater number of patients.

A prospective, randomized, controlled trial comparing three different gonadotropin regimens in oocyte donors: ovarian response, in vitro fertilization outcome, and analysis of cost minimization.

OBJECTIVE: To compare the efficacy of three different gonadotropin regimens in an oocyte donation program. The analysis of cost minimization also was evaluated. DESIGN: Prospective, randomized, controlled study. SETTING: Instituto Universitario-IVI, Valencia, Spain. PATIENT(S): One thousand twenty-eight donors undergoing a GnRH agonist protocol were assigned randomly to one of three groups: group 1 (n=346), only recombinant FSH (rFSH); group 2 (n=333), only highly purified menotropin (HP-hMG); and group 3 (n=349), rFSH plus HP-hMG. One thousand seventy-nine oocyte recipients. INTERVENTION(S): Controlled ovarian stimulation. MAIN OUTCOME MEASURE(S): Controlled ovarian stimulation parameters, IVF outcome, and cost analysis. RESULT(S): No differences were found among the groups with respect to days of stimulation, gonadotropin dose, final E2 and P levels, number of oocytes retrieved, and cancellation rate. Similarly, there were no differences among the groups in terms of embryo development parameters. Moreover, implantation, pregnancy, and miscarriage rates with the three regimens were similar. However, the cost of rFSH was greater than that of the other protocols. CONCLUSION(S): This study suggests that in the GnRH agonist protocol the three different gonadotropin regimens evaluated herein are equally effective. Protocols using HP-hMG would appear to be the best in terms of cost-effectiveness in an oocyte donation program.

Assessment of ovarian and uterine blood flow by transvaginal color Doppler in ovarian-stimulated women: correlation with the number of follicles and steroid hormone levels.

OBJECTIVE: To study the changes that occur in vascular resistance to flow in the utero-ovarian circulation and their correlation with the number of follicles and steroid hormone levels in patients undergoing ovarian stimulation with gonadotropin. DESIGN: In a prospective study, the impedance to flow in the intraovarian and uterine vessels was measured by means of transvaginal color flow Doppler imaging throughout the cycle. SETTING: University-based IVF program. PATIENTS: Eleven infertile patients undergoing ovarian stimulation with gonadotropin in preparation for IVF and ET. MAIN OUTCOME MEASURES: Intraovarian, uterine, and arcuate artery blood flow velocity waveforms, follicular growth, and serum E2 and P concentrations throughout the cycle. RESULTS: Pulsatility index (PI) of the intraovarian blood vessels and uterine artery decreased gradually during the follicular and luteal phase. The PI of the arcuate artery did not change significantly. The PI of the intraovarian blood vessels correlated with the number of follicles (> 15 mm; day of hCG). Serum E2 concentrations but not P demonstrated negative linear correlation with the PI of the intraovarian vessels and uterine artery. CONCLUSIONS: Induced cycles are associated with decreased impedance to blood flow in the utero-ovarian circulation. Intraovarian PI correlates negatively at each stage of the cycle with the eventual number of preovulatory follicles. Little or no changes are observed when the response to ovarian stimulation is poor.

Are factors that influence oocyte fertilization also predictive? An assessment of 148 cycles of in vitro fertilization without gonadotropin stimulation.

Fertilization characteristics of 152 consecutively obtained oocytes in an in vitro fertilization (IVF) program employing only natural and clomiphene citrate-induced cycles were retrospectively analyzed. Fertilization occurred significantly more often (1) in women with tubal infertility, (2) in spontaneous cycles, and (3) in cases of secondary infertility. Grade I sperm motility from the original semen sample and the duration of infertility were also significant influencing factors. A similar sperm correlate was not identified on samples after sperm migration. Preovulatory follicular fluid steroids, progesterone (P), estradiol (E2), E2:P ratio, and luteinizing hormone (LH), as well as baseline plasma LH and the magnitude of the LH surge did not correlate with fertilization. However, when the identified factors were used to predict fertilization (discriminant analysis), only 58.3% of oocytes were correctly classified. This data supports the concept of performing IVF as a test in its own right.