Gn-RH antagonists in intrauterine insemination: the weekend-free protocol.

OBJECTIVE: To compare the results of intrauterine insemination (IUI) when GnRH antagonist was added-to avoid IUI on weekend-with those obtained with the standard IUI protocol. STUDY DESIGN: In an IUI program under ovarian stimulation with gonadotropins when one or more follicles of 15-16 mm were seen, if it was not possible for logistic reasons (weekend) to perform the insemination 72 h later, GnRH antagonist was administered until human chorionic gonadotropin (hCG) administration. The IUI was performed on Monday. We compared the results of this IUI "weekend-free'' group with our results in standard IUI cycles, where IUI was performed 36-38 h after reaching optimal follicular growth. RESULTS: Both groups were comparable regarding the main demographic parameters, except for higher estradiol levels, due to the prolonging ovarian stimulation. The per cycle pregnancy rate (PR) were very similar in both groups: 15.7% in the weekend-free IUI versus 16.5% in standard IUI. The multiple pregnancy rate and the hyperstimulation rate were also similar. A non-significant trend to higher high-order multiple pregnancy was observed in the weekend-free IUI. CONCLUSIONS: In IUI cycles under ovarian suprastimulation with gonadotrophins, the use of GnRH antagonist allows the manipulation of the follicular development in such a way that it is possible to avoid inseminations on the weekends, without apparently reducing the PR.

The implantation of every embryo facilitates the chances of the remaining embryos to implant in an IVF programme: a mathematical model to predict pregnancy and multiple pregnancy rates.

BACKGROUND: We aimed to assess the validity of a theoretical mathematical model to predict the pregnancy rate and the multiple pregnancy rate in IVF/oocyte donation programmes on the basis of the implantation rate and the number of transferred embryos. METHODS: A total of 1835 embryo transfers corresponding to three different programmes in two centres with different implantation rates were analysed. Pregnancy and multiple pregnancy rates observed in the aforementioned programmes were compared with those obtained following different mathematical models. Four models were tested: binomial model, ground model, maternal variability model and collaborative model. The goodness of fit was performed by means of the maximum likelihood fit method. RESULTS: The binomial model could not predict the pregnancy rate, and especially the multiple pregnancy rate. The multiple pregnancy rate predicted following the binomial model was much lower than observed, up to 40-fold reduced. Ground model and maternal variability model adjusted to the data with more precision, but were still not accurate. Finally, the collaborative model reproduced with very great accuracy both pregnancy rate and the multiple pregnancy rate. A collaborative parameter of 22% was found, implying that the implantation probability of each embryo is increased by 22% for every embryo previously implanted. CONCLUSIONS: Embryonic implantation does not follow a binomial law, showing that the implantation is not independent from the number of embryos implanted. The best fit to the data is obtained following a collaborative model by which the implantation of one embryo is facilitated by the implantation of other embryo(s). The mathematical formula of the collaborative model predicts very accurately the pregnancy rate and the multiple pregnancy rate in IVF/oocyte donation programmes, based on the implantation rate of this specific programme and the number of embryos transferred up to five embryos. We recommend using the aforementioned formula to quantify the pregnancy rate and the risk of multiple pregnancy in the counselling of the infertile couple at embryo transfer. Such a formula is freely available at www.ifca.unican.es/matorras/mathpreg/.

One versus two inseminations per cycle in intrauterine insemination with sperm from patients' husbands: a systematic review of the literature.

OBJECTIVE: To study the efficacy of performing two inseminations per cycle in IUI with husband's sperm compared with one insemination per cycle. DESIGN: Meta-analysis. SETTING: Randomized and prospective trials comparing two inseminations vs. one insemination per cycle in IUI with husband's sperm, retrieved by MEDLINE and Cochrane Library searches (1966-2001) and a manual search of the abstracts of the European Society of Human Reproduction and Embryology and American Society for Reproductive Medicine annual meetings (1990-2001). PATIENT(S): A total of 865 patients underwent 1156 cycles of IUI with husband's sperm. INTERVENTION(S): After different ovarian stimulation protocols, one or two inseminations were performed. MAIN OUTCOME MEASURE(S): Pregnancy rate per cycle. Detected studies were tested for homogeneity. Because heterogeneity was observed, DerSimonian-Laird relative risk with alleatory effects was used. RESULT(S): Six randomized and prospective trials involving 865 patients and 1156 cycles were identified. There was remarkable heterogeneity among the different studies concerning methodology, especially regarding ovarian cycle management and the timing of inseminations. Although the pregnancy rate per cycle was somewhat higher in the two-inseminations-per-cycle group (14.9% vs. 11.4%), there were no statistically significant differences (relative risk = 1.34; 95% confidence interval 0.90-1.99). CONCLUSION(S): No significant differences were observed when two inseminations per cycle were performed, compared with one insemination. There was great heterogeneity concerning ovarian management and insemination timing. This heterogeneity hampered the analysis. We detected a better pregnancy rate with two inseminations vs. one insemination when clomiphene citrate with or without gonadotropins and 5000 IU of hCG were used. More studies are necessary to ascertain whether this is true or merely an artifact from the multiple subgroups analysis.

Ovulation induction with a starting dose of 50 IU of recombinant follicle stimulating hormone in WHO group II anovulatory women: the IO-50 study, a prospective, observational, multicentre, open trial.

OBJECTIVE: To assess the efficacy and safety in clinical practice of a low dose regimen of 50 IU of recombinant follicle stimulating hormone in induction of ovulation. DESIGN: Prospective, observational, non-comparative, open, multicentre study. SETTING: Eighty-eight infertility clinics and teaching hospital fertility units throughout Spain. POPULATION: Women with normogonadotrophic chronic anovulation (WHO group II) with or without echographic diagnosis of polycystic ovary syndrome. METHODS: Low dose step-up protocol of recombinant follicle stimulating hormone administration (follitropin beta, Puregon) with a starting dose of 50 IU and weekly increments according to follicular response monitored prospectively by transvaginal ultrasonography. Patients were followed for a minimum of one cycle and a maximum of six. MAIN OUTCOME MEASURES: Rate and size of follicular growth, cumulative ovulation rate, follicle stimulating hormone doses and duration of treatment, pregnancy and cycle cancellation rate, ovarian hyperstimulation syndrome and multiple pregnancy. RESULTS: A total of 945 treatment cycles were evaluated. In 817 cycles, ovulation was induced with human chorionic gonadotrophin (hCG) and in 501 (61.3%) unifollicular development (a follicle of > or =18 mm) was achieved. A total of 128 cycles (13.5%) were cancelled because of ovarian hyper-responsiveness or spontaneous ovulation. The cumulative ovulation rate (confirmed by mid-luteal serum progesterone concentrations) after six treatment cycles was 84%. There were 136 clinical pregnancies (14.4% pregnancies per cycle). The cumulative pregnancy rate after six treatment cycles was 53.1%. Eight twin pregnancies occurred. Thirteen women miscarried and there were two cases of ectopic pregnancies. The median of average daily doses of follitropin beta in all cycles was 50 IU. Between 68% and 86% of patients received treatment with follitropin beta for a maximum of 14 days. Ovarian hyperstimulation syndrome occurred in 64 (6.8%) cases but no case of severe ovarian hyperstimulation developed. CONCLUSIONS: Low dose regimen of 50 IU of recombinant follicle stimulating hormone (Puregon) is efficient, safe and well tolerated for inducing follicular development in WHO group II anovulatory women.

Converting an IVF cycle to IUI in low responders with at least 2 follicles.

OBJECTIVE: To assess the utility of transforming an in vitro fertilization (IVF) cycle with low ovarian response to an intrauterine insemination (IUI) cycle. STUDY DESIGN: The inclusion criteria were women undergoing IVF because of idiopathic infertility, a mild to moderate male factor or IUI failure, with at least 1 normal, patent tube. When ovarian stimulation produced 2-4 follicles > or = 18 mm, the IVF cycle was converted to an IUI cycle. In cases with 4 follicles, estradiol had to be < 800 pg/mL. A total of 57 cycles were analyzed. RESULTS: The clinical pregnancy rate (PR) was 14.0% (8/57) in IVF cycles converted to IUI vs. 17.3% in our general IUI population (240/1,389). Converted cycles were associated with longer ovarian stimulation and with lower estradiol levels and less mature follicles than was IUI in the general population. There was a trend toward higher PR in women starting ovarian stimulation with 225 IU of gonadotropins (18.2%) than in those starting with higher doses (8.6%) (P > .05). CONCLUSION: In IVF low responders with at least 1 normal, patent tube when 2-4 follicles are observed, converting the IVF cycle to an IUI cycle yields a PR of 14.0%. This option should be considered in the management of low responders, especially those not stimulated with high doses of gonadotropins.

The use of urinary gonadotrophins should be discouraged.

In view of concerns regarding the potential presence and infectivity of prion proteins in human urinary gonadotrophin preparations, together with the availability of both recombinant FSH and recombinant LH, it is argued that the use of urinary gonadotrophins should be discouraged.

Recurrence of endometriosis in women with bilateral adnexectomy (with or without total hysterectomy) who received hormone replacement therapy.

OBJECTIVE: To estimate the risk of recurrence after administration of hormone replacement therapy (HRT) among women who have had endometriosis and who underwent bilateral salpingo-oophorectomy (BSO). DESIGN: Prospective randomized trial (115 women receiving HRT and 57 not receiving HRT). SETTING; Public university hospital. PATIENT(S): Women with a histologic diagnosis of endometriosis in whom BSO was performed; 91.8% had a total hysterectomy. INTERVENTION(S): Periodical clinical examination, vaginal ultrasound, and CA-125 levels; surgical evaluation and histologic study. MAIN OUTCOME MEASURE(S): Recurrence rate, prognostic factors, and a mean follow-up time of 45 months. RESULT(S): There was no recurrence among women who did not receive HRT, versus a 3.5% rate (4 out of 115), or 0.9% per year, in women who received HRT. Two recurrences required abdominal surgery. There was one additional patient who required surgery, but the relationship to the endometriosis recurrence was controversial. Among women receiving HRT, the following risk factors were detected: peritoneal involvement > 3 cm (2.4% recurrence per year vs. 0.3%) and incomplete surgery (22.2% per patient vs. 1.9%). CONCLUSION(S): Patients with a history of endometriosis in whom total hysterectomy and bilateral salpingo-oophorectomy have been performed have a low risk of recurrence when HRT is administered. In those patients, HRT is a reasonable option. However, in cases with peritoneal involvement > 3 cm, the recurrence rate makes HRT a controversial option; if HRT is indicated, it should be monitored closely.