Should intrauterine inseminations still be proposed in cases of unexplained infertility? Retrospective study and literature review.

OBJECTIVE: Unexplained infertility is defined by the absence of identifiable causes of infertility. The results of randomized studies and meta-analysis regarding the treatment of unexplained infertility are discordant due to methodological problems. DESIGN: The aim of this study is to compare the clinical pregnancy rate per cycle (CPR/c) in IUI and IVF/ICSI in cases of unexplained infertility, according to the woman's age group and to identify the factors which predict success. INTERVENTIONS: We performed a retrospective study in two ART centers, comparing overall clinical pregnancy, ongoing pregnancy and live birth rates in IVF/ICSI and IUI. We also compared pregnancy and birth rates according to different female age groups. RESULTS: 855 IVF/ICSI and 804 IUI cycles were compared. We found a significant difference (p < 0.001) in the pregnancy and live birth rates per cycle between IUI and IVF/ICSI, overall and in the different female age groups, except in women aged 40 and over. The greatest chances of pregnancy with IUI are found in women with secondary unexplained infertility, during the first two cycles and with a bi-follicular response to stimulation. In IVF/ICSI, pregnancy rates are higher in women with secondary unexplained infertility, in the first two cycles, in IVF and in women receiving a transfer of two embryos regardless of the embryonic stage. CONCLUSION: We recommend IVF/ICSI treatment rather than IUI for unexplained infertility (OR CPR/c 4.20 with 95% CI [3.72-4.68]). This is in accordance with NICE, which advises the use of IVF after 2 years.

Can Ratios Between Prognostic Factors Predict the Clinical Pregnancy Rate in an IVF/ICSI Program with a GnRH Agonist-FSH/hMG Protocol? An Assessment of 2421 Embryo Transfers, and a Review of the Literature.

None of the models developed in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is sufficiently good predictors of pregnancy. The aim of this study was to determine whether ratios between prognostic factors could predict the clinical pregnancy rate in IVF/ICSI. We analyzed IVF/ICSI cycles (based on long GnRH agonist-FSH protocols) at two ART centers (the second to validate externally the data). The ratios studied were (i) the total FSH dose divided by the serum estradiol level on the hCG trigger day, (ii) the total FSH dose divided by the number of mature oocytes, (iii) the serum estradiol level on the trigger day divided by the number of mature oocytes, (iv) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day, (v) the serum estradiol level on the trigger day divided by the number of mature oocytes and then by the number of grade 1 or 2 embryos obtained, and (vi) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day and then by the number of grade 1 or 2 embryos obtained. The analysis covered 2421 IVF/ICSI cycles with an embryo transfer, leading to 753 clinical pregnancies (31.1% per transfer). Four ratios were significantly predictive in both centers; their discriminant power remained moderate (area under the receiver operating characteristic curve between 0.574 and 0.610). In contrast, the models' calibration was excellent (coefficients: 0.943-0.978; p < 0.001). Our ratios were no better than existing models in IVF/ICSI programs. In fact, a strongly discriminant predictive model will be probably never be obtained, given the many factors that influence the occurrence of a pregnancy.

Comparison of two preventive treatments for patients with recurrent miscarriages carrying a C677T methylenetetrahydrofolate reductase mutation: 5-year experience.

Objective To investigate the effect of anticoagulant treatment on pregnancy outcomes in patients with previous recurrent miscarriages (RM) who carry a methylenetetrahydrofolate reductase ( MTHFR) gene mutation. Methods In this longitudinal retrospective study, patients with RM were treated during pregnancy with either: (i) 100 mg/day aspirin and 5 mg/day folic acid (group 1); or the same protocol plus 0.4 mg/day enoxaparin (group 2). An age-matched group of triparous women without RM or thrombophilia was used as the control group (group 3). Results This study enrolled 246 women with RM (123 per treatment group) and age-matched controls ( n = 117). The delivery rate was significantly lower in group 1 than group 2 (46.3% versus 79.7%, respectively). The miscarriage rate was significantly lower in group 2 compared with group 1 (20.3% versus 51.2%, respectively). In the control group 3, the delivery rate was 86.3% and the miscarriage rate was 12.8%. Conclusion Treatment with low-dose aspirin, enoxaparin and folic acid was the most effective therapy in women with RM who carried a C677T MTHFR mutation.

Effect of Gonadotropin Types and Indications on Homologous Intrauterine Insemination Success: A Study from 1251 Cycles and a Review of the Literature.

OBJECTIVE: To evaluate the IUI success factors relative to controlled ovarian stimulation (COS) and infertility type, this retrospective cohort study included 1251 couples undergoing homologous IUI. RESULTS: We achieved 13% clinical pregnancies and 11% live births. COS and infertility type do not have significant effect on IUI clinical outcomes with unstable intervention of various couples' parameters, including the female age, the IUI attempt rank, and the sperm quality. CONCLUSION: Further, the COS used seemed a weak predictor for IUI success; therefore, the indications need more discussion, especially in unexplained infertility cases involving various factors. Indeed, the fourth IUI attempt, the female age over 40 years, and the total motile sperm count <5 × 106 were critical in decreasing the positive clinical outcomes of IUI. Those parameter cut-offs necessitate a larger analysis to give infertile couples more chances through IUI before carrying out other ART techniques.

Comparative prospective study of 2 ovarian stimulation protocols in poor responders: effect on implantation rate and ongoing pregnancy.

BACKGROUND: In patients treated with IVF, the incidence of poor ovarian response (POR) after ovarian stimulation varies from 9 to 25 %. However, at present, there are no clear guidelines for treating these poor responders. This study was designed to compare two different ovarian stimulation protocols and addresses future perspectives in the management of these unfortunate patients. METHOD: Four hundred and forty poor responders were studied during their second IVF cycle. They had all failed to become pregnant during their first IVF cycle where the long GnRH-agonist stimulation protocol (P1) was used. Patients were prospectively randomly assigned to 2 protocol groups (P2 or P3, 220 patients in each arm) at the start of ovarian stimulation according to the order of entry into the study including one patient per each stimulation protocols: The P2 group was treated with a contraceptive pill + flare-up GnRH-agonist protocol and the P3 group with the GnRH-antagonist protocol. The ovarian stimulation characteristics as well as the clinical and ongoing pregnancy rates were compared. RESULT(S): Although the numbers of embryos obtained and transferred were significantly higher with the P2 protocol, the implantation and ongoing pregnancy rates per transfer were the same in the two studied groups (8.9 % versus 14.6 % and 8.4 % versus 14.2 % for the P2 and P3 protocols, respectively). Good prognostic factors for ongoing pregnancy with both protocols were: a maternal age <36, no tobacco consumption, a total dose of gonadotropins injection <5000 IU and an endometrial thickness >10 mm. CONCLUSION(S): In poorly responding patients treated with IVF, the implantation and ongoing pregnancy rates per transfer were not significantly different between the two protocols studied: contraceptive pill + flare-up GnRH-agonist protocol and the GnRH-antagonist protocol. It is suggested that current strategies for the management of poor responders be reconsidered in the light of the potential contribution of age and the effect of life style changes on fertility potential. A customised policy of ovarian stimulation in these patients including mild stimulation protocols, sequential IVF cycles, oocytes-embryos freeze all protocols and blastocyst transfers after screening may improve the clinical outcome.

[Intrauterine insemination]. / Une étape nécessaire dans la prise en charge du couple infertile: Inséminations intra-utérines.

The intrauterine insemination with husband's sperm is an assisted reproductive technologie, as proposed in the case of cervical infertility, moderate male infertility, dysovulation, mild or moderate endometriosis or unexplained infertility. In the last three indications the ovarian stimulation is necessary. The couple demographic criteria (age of both partners, lifestyle, duration of infertility) and the results of the infertility evaluation (ovarian reserve, uterus, spermogram-spermocytogram) increase the chances of pregnancy by intrauterine insemination with husband's sperm and reduce the risk of multiple pregnancies. Pregnancy rates observed ranged from 8 to 20% per cycle according to indications.

[Declining fertility with age]. / Informer les couples. Baisse de la fertilité avec l'age.

The will to be a mother at a late age has become a real problem of society for many reasons, first and foremost because of efficient birth control, long studies and second matrimonies. In front of these still young women but quite "old" for maternity, practitioners specialized in medically assisted procreation (MAP) are often helpless, specially because most of the patients think that the MAP will be able to cure the natural decline of fertility. However, MAP's procedures cannot correct the decrease of pregnancies' rates and the increase of spontaneous miscarriages linked with the age. One of the first aims of consulting-physicians should be to give patients proper advice about fertility decline, so that women could run their life, aware of these facts.

Predictive factors for pregnancy after intrauterine insemination (IUI): an analysis of 1038 cycles and a review of the literature.

OBJECTIVE: To determine the predictive factors for pregnancy after IUI. DESIGN: Retrospective study. SETTING: A single university medical center. PATIENT(S): One thousand thirty-eight IUI cycles in 353 couples were studied between 2002 and 2005. INTERVENTION(S): Ovarian stimulation via SC injection of FSH or hMG was performed daily; IUI was then performed 36 hours after triggering ovulation if at least one follicle measuring >16 mm and an endometrial thickness of >7 mm (with triple-line development) were obtained. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates were analyzed according to the woman's age, the type of infertility, the spermogram characteristics, the total motile spermatozoa (TMS) count, the E(2) level before hCG injection, and the number of mature follicles. RESULT(S): The couple with the best chance of pregnancy can be described as follows: an under 30 woman with cervical or anovulatory infertility and a man with a TMS >or=5 million spermatozoa. The "ideal" stimulation cycle enables the recruitment of two follicles measuring >16 mm with an E(2) concentration >500 pg/mL on the day of hCG administration. The best results are obtained when IUI is performed using a soft catheter. CONCLUSION(S): This study enabled the characterization of many prognostic factors for pregnancy and particularly those for women at risk of multiple pregnancies after IUI.

Physiopathology of human embryonic implantation: clinical incidences.

Embryo implantation consists of a series of events promoting the invasion of the endometrium and then the uterine arterial system by the extra-embryonic trophoblast. In order for this semi-heterologous implantation to succeed, the endometrium has to first undergo a number of structural and biochemical changes (decidualization). The decidua's various constituents subsequently play a role in the embryonic implantation. The third step is the transformation of the uterine vascular system and the growth of the placenta, which will provide the foetoplacental unit with nutrients. Several physiopathological aspects will be discussed: 1) the implantation window, regulated by maternal and embryonic hormonal secretions and thus influenced by any defects in the latter: dysharmonic luteal phase, 21-hydroxylase block, abnormal integrin expression, 2) the successive trophoblast invasions of uterine vessels which, when defective, lead to early embryo loss or late-onset vascular pathologies, as preeclampsia, 3) the pregnancy's immunological equilibrium, with a spontaneously tolerated semi-allogeneic implant, 4) the impact of pro-coagulant factors (thrombophilia) on the pregnancy's progression, 5) the environment of the uterus, ranging from hydrosalpinx to uterine contractions. In summary, the least anatomical or physiological perturbation can interfere with human embryonic implantation - a very particular phenomenon and a true biological paradox.