[Failure of in vitro fertilization: prognosis criteriae]

Background: age, obesity and increased FSH serum level in women are prognosis criteriae associated with decreased fertility and adverse Assisted Reproductive Technologies [ART] outcomes

Objective: To assess the effect of age, FSH and BMI on pregnancy rate in ICSI

Methods: A retrospective and comparative study of 500 women who underwent ICSI cycle during the study period from January 2004 to December 2005. Age, FSH and BMI were compared in two groups of patients: Those achieving a pregnancy: The "pregnancy+" group and those failing to have a pregnancy: The "pregnancy-"group. For each of previous parameters ROC curve and logistic regression study were performed

Results: age was significantly lower in "pregnancy+" group [32,4 +/- 3,9 years vs 33,7 +/- 4,8 ans ; p=0,005]. Analysis of ROC curve and logistic regression study show that for age, the most discriminative cut-off for predicting pregnancy is 38 years [Se=7,5%, Sp=75,6%] [AUC=0,572; p=0,02] [OR=2,1 ; LR+=6,7 ;IC[1 ;1,4] ; p0,009]. FSH was significantly lower in "pregnancy+" group [5,5 +/- 1,8UI /L vs 6,2 +/- 3UI/L, p=0,003]. Analysis of ROC curve and logistic regression study show that for FSH, the most discriminative cut-off for predicting pregnancy is 9UI/L [Se=3,7%, Sp=85.2%] [AUC=0,539 ; p=0,03] [OR=3,6; IC[1,4 ;9,3]; LR+ =10,1; p=0,003]. BMI was also significantly lower in "pregnancy+" group [24,7 +/- 3,6 kgm-2 vs 27,1 +/- 4,5 kgm-2 ; p<10[-3]]. The most discriminative cut-off for predicting pregnancy is 25,4 kgm- 2 [Se=31,7%, Sp=33,3%] [AUC=0,663 ; p<10[-3]] [OR=4; IC[2,1 ;7,7]; LR+ =19,38; p<10[-3]]

Conclusion: age, FSH and BMI affect markedly the prognosis of ICSI. We found significantly lower Pregnancy rates in older women [> 38 years], in women with elevated FSH [> 9UI/L] or elevated BMI [> 25,4 kgm-2]. Our results can be used when counseling and before including patients in an IVF program, to give them probability of success and weight loss required to optimize chances of pregnancy

[Impact of gamete cell quality on the outcome of intracytoplasmic sperm injection]

Background: the quality of the gametes used for an intracytoplasmic microinjection of spermatozoïde is a significant factor which can influence pregnancy rates

Aim: To assess the effect of conventional sperm parameters, origin of spermatozoa and oocyte quality on pregnancy rate in ICSI

Methods: A retrospective and comparative study of 500 women who underwent ICSI cycle during the study period from January 2004 to December 2005. Conventional sperm parameters [count, motility and morphology] and oocyte quality [mature and immatures oocytes] was compared in two groups of patients: Those achieving a pregnancy: The "pregnancy+" group and those failing to have a pregnancy: The "pregnancy-" group

Results: Among the conventional sperm parameters, only spermatozoa count after preparation was significantly higher in "pregnancy+" group [p=0,02]. We found significantly more pregnancies in ejaculated and epididymal sperm groups than in the testicular one [p<10-3]. The number of oocyte retrieved was significantly higher in "pregnancy+" group [13,9 +/- 7 vs 10,6 +/- 7,6 ; p<10-3] with mainly mature oocyte [metaphaseII] [9,1 +/- 5,5 vs 6,6 +/- 5,4 ; p<10-3]. Analysis of ROC curve and logistic regression study show that for mature oocyte, the most discriminative cut-off for predicting pregnancy is 4 [OR=2,1 ; LR+=6,7 ;IC[1 ;1,4] ; p0,009]

Conclusion: Conventional parameters of ejaculated sperm have almost no influence on pregnancy rates in ICSI. Testicular sperm seem to have worse results. The number of oocytes retrieved and the proportion of mature oocytes [metaphaseII] affect markedly the prognosis

[Short vs long agonist protocols in poor responders undergoing IVF]

Compare among poor responders: stimulation results, laboratory parameters and the final IVF results by assessing 2 different stimulation protocols: the long agonist protocol and the short agonist protocol. An analytical retrospective study carried out over of period of 2 years: January 2006 and December 2007. During this period, a total of 1192 IVF cycles of ICSI type were performed in 892 patients. Inclusion criteria: short agonist or antagonist stimulated patients protocols and presenting two of the three following criteria: 1- Patients aged more than 38 years with an FSH plasmatic rate on the 3rd day of the cycle 9.5 UI/ml. 2- Antral follicle count [AFC] 5 for both ovaries. 3- Failure of anterior ovary stimulation: abandonment of cycle or ‹ 3 oocytes at data collection in a previous cycle. Exclusion criteria: PCOS or single ovary. 65 patients, undergoing 92 attempts of ICSI cycles have been included in this study. Long agonist protocol was performed in 48 cases and Short agonist protocol was performed in 44 cycles. Both groups were comparable as to age [40,09 +/- 6, 59 vs 41, 04 +/- 1,71 years; NS], BMI [25,2 +/- 3,92 vs 25,35 +/- 4,09 Kgm-2 ; NS], infertility type [primary 41% vs 59%;NS ; ou secondary 58% vs 40,9% ; NS], FSH [9,98 +/- 2,42 vs 10,01 +/- 2,75 ; NS] and antral follicle count on day 3 [4,13 +/- 1,12 vs 3,8 +/- 1,16 FA ; NS]. The estradiol rate, dosed on the onset day was significantly higher in the short protocol group [1534,27 +/- 1034,34 vs 1133,31 +/- 1053,58 pg/ml; p=0.034]. However, the consumed quantity of gonadotrophins was lower in the short protocol group [1550 +/- 235,45 vs 1725,55 +/- 450,35 UI, p=0.01]. A total of 13 cycles was stopped: 9 times for the long protocol [18.75 %] and 4 times for the short protocol [9.09 %] with statistically significant difference. The number of collected oocytes was significantly higher in the short protocol [7,64 +/- 3,70 vs 4,55 +/- 2,01, P<0.001]. We significantly obtained more embryos in the short protocol [4,31 +/- 2,9 vs 2,16 +/- 2,2 embryos ; p<0,001]. With higher number of grade 1 embryos [2,61 vs 1,14 embryons; p<0.001].The results in terms of pregnancy and living births show no significant difference between the 2 groups. The short protocol is more suited to the profile of ovarian poor responders. The long protocol standard has no place in poor responders. However, the long micro dose protocol and the long degressed micro dose protocol yield results at least equivalent to the short protocol

[ usefulness of elastase measurement in the sperm for the diagnosis of urogenital male inflammation and infection]

Genital tract inflammation is a frequent cause of infertility among men, usually clinically silent with only leukocytospermia defined as the presence of white blood cells [WBC]>1.10[6]/ml in semen. During the inflammation process, granulocytes discharge large amounts of proteases such as elastase. The elastase linked to its inhibitor in the form of a complex the elastase alpha1-protease inhibitor in semen is suggested as a potential marker of genital tract inflammation. To assess the measurement of elastase as a biomarker of genital tract inflammation by comparing this technique with the detection of leukocytospermia according to the WHO guidelines. methods: This study interested 83 infertile men attending the andrology center for semen analysis. Leukocytospermia was assessed by a peroxydase test and elastase concentration by immunoassay in the seminal plasma. An elevated elastase was found in 38% of men. A similarity was found between leukocytospermia and elastase in 79% of cases, kappa coefficient concordance with leukocytospermia is good [0.78]. The sensitivity of the elastase is 100%, the specificity= 75%. The positive predictive value is 47%, the negative predictive value is 100% with a Youden index=0.75. All patients with leukocytospermia>1.106/ml had an elastase>250ng/ml, 73% of them a concentration>1000 ng/ml. In the group of patients with no leucocytospermia, 75% had elastase<250ng/ml, 21% had concentration between 250 and 1000ng/ml and 4% [3 patients] a concentration>1000ng/ml. Seminal elastase is a more sensitive marker than leucocytospermia in the diagnosis of male urogenital inflammation and infection

[Basal fsh level is only predictive of the quantitative aspect of the ovarian response]

Determination FSH and LH at day 3 of the menstrual cycle predicts the response to stimulation. To evaluate the value of FSH and LH measurements compared with women's age in predicting qualitative and quantitative ovarian response to gonadotrophin stimulation. 305 patients underwent at least one intra cytoplasmic sperm injection [ICSI] cycle. The levels of FSH and LH at day 3 were determined in an earlier cycle. A good quantitative ovarian response was defined as [3]3 oocytes retrieved and 3 embryos obtained. A good qualitative ovarian response was defined as a percentage of mature oocytes [3] 75% and immature ones²15% of the total number of oocytes retrieved with at least one top quality embryo obtained. Receiver operating characteristic [ROC] curves were generated for FSH, LH and female age. FSH is better than female age in predicting the number of oocytes retrieved [respectively ROCAUC=0.77, p=10-3 versus ROCAUC=0.73, p=10-3] and the number of embryos obtained [ROCAUC=0.69, p=10-3 versus ROCAUC=0.66, p=10-3]. LH is non predictive. None of the three tested parameters was predictive of the fertilization and pregnancy rates. An FSH cutoff was calculated and a value of 7.8mUI/ml is associated with a sensitivity of 73% and a specificity of 70% for the prediction of ovarian response to controlled stimulation. Basal FSH level predicts good quantitative rather than qualitative response. LH is non predictive. FSH and LH do not predict pregnancy rate. Patients having high FSH levels should not be excluded from IVF/ICSI treatment

Clinicals and biologicals aspects of ICSI cycles on polycystic ovary syndrome patients

To analyse clinical and biological pecularities of Polycystics Ovarian Syndrome[PCOS] patients enrolled on ICSI cycles and compare them to normo-ovulatory women. 100 controlled ovarian stimulation cycles for ICSI in women with PCOS and 200 cycles in normo-ovulatory women. There was no significant difference in term of cancellation rate [5,5% in PCOS group vs 5%;NS]. The mean number of follicles was higher in patients with PCOS [18,1 +/- 8,5 vs 9,4 +/- 5,5;p<0,05], Oocyte mature rate and fertilization rate were higher in PCOS group [67% vs 52%; p<0,05] [75% vs 63,7%; p<0,05] respectively. Grade 1 Embryo rate was significantly higher in PCOS group [69% vs 53%; p<0,05]. Implantation rate [16,6% vs 12,1%; NS] and clinical pregnancy rate per transfer [3 1,5% vs 22,2%; NS] did not differ statistically in the two groups. Miscarriage rate was higher in PCOS group but this did not reach the statistical significance [20% vs 7,1%; NS]. 11 cases of Ovarian hyperstimulation syndrome occurred in PCOS group versus 4 on normo-ovulatory group. Use of ICSI as fertilization technique was correlated with good biologic parameters on PCOS patients with better fertilization rate and embryo quality and similar pregnancy rate comparing to normo-ovulatory women. However, it still be great concern about high risk of miscarriages and Hyperstimulation ovarian syndrome

[ retrospective study of 339 ICSI cycles: assessment of the two first years of activity of the assisted reproductive technology's center of Aziza Othmana's hospital]

Intracytoplasmic sperm injection [ICSI] is a micro-manipulation-assisted fertilization, whereby one spermatozoon is injected into the oocyte cytoplasm. Initially, ICSI was the treatment of choice for male factor infertility. However, because of the high fertilization and pregnancy rates achieved with this technique, the scope of the procedure has been widened to include couples with other causes of infertility. The aim of this study was to study the progression of the activity of the assisted reproductive technology's center of Aziza Othmana's Hospital and the ICSI results during the first two years. Our study included 269 infertile couples who underwent 339 ICSI cycles between 1st May 2001 and 30 April 2003. Cycles with no oocytes obtained at the follicular aspiration and women aged over 40 years were excluded from this study. The number of ICSI cycles progressed in our center: 150 ICSI cycles in the 1st year, 189 ICSI cycles in the 2nd year. The mean number of picked-up oocytes was 8,8 +/- 5,6. The fertilization rate was 62. The mean number of transferred embryos was 3,1 +/- 1,5. The pregnancy rate per transfer was 32,4%. The miscarriage rate was 28,4%. The take home baby rate was 67,9%. The number of couples undergoing ICSI cycles in our center is increasing. The fertilization rates and pregnancy rates in our center are similar to those published in the literature

[Increased risk of early pregnancy loss and lower live birth rate with GNRH antagonist vs long GNRH agonist protocol in PCOS women undergoing controlled ovarian hyperstimulation]

To compare standard long GnRH agonist protocol [Tripnorelin] anti GnRH antagonist regimens [Cetrorelix] in polycystic ovary syndrome [PCOS] patients undergoing controlled ovarian stimulation [COS] for ICSI cycles. Retrospective case-control study. 106 POS patients undergoing COS for ICSI with long GnRH agonist protocol [Tripnorelin] were matched with age and BMI to 106 PCOS patients undergoing COS for ICSI with GnRH antagonist [Cetrorelix] during the same period. Ovarian stimulation with recombinant follicle stimulating hormone [rFSH] was used in the two groups. Oral contraceptive pill pretreatment was used in all patients undergoing ovarian stimulation using GnRH antagonists. ICSI was performed for male infertility in all casts. The main outcome measures evaluated were: cancellation of the cycles, number of aspirated follicles, oocyte maturity, fertilization rate, Embryo quality, pregnancy and implantation rates, clinical abortion rate, multiple pregnancy rate and the live birth rate rate. Kchi2 teat and t Student test were used for differences between normo-ovulatory and PCOS patients and the limit of significantly was net at p<0.0S. There. was no significant difference in term of cancellation rant [2.8%vs 1.8%; NS], Duration of gonadotrophin stimulation [9,7 +/- 0,7 vs 11,2 +/- 1,9 days; p<0,001] and gonadotrophin consumption [2209.0 +/- S4S Vs 1411,1 +/- 217,9 1.11: p<0,001] were significantly decreased with GnRH antagonist. The mean oestradiol level on the triggering day was significantly higher in the agonist group [3347,85 +/- 99 vs 2354,45 +/- 839; p<0,001]. A fall in LH level of a 50%from sitmulation days [S8] to S1was observed in GnRH antagonist group. Risk of ovarian] hyperstimulation syndrome [OHSS] was significantly decreased with GnRH antagonist [1.8%vs 10.7%; p=0.01]. The mean number of retrival oncytes [15.9 +/- 5,9 vs 17.3 +/- 8.3; ns] and the mean number of mature oncytes [11.43 +/- 4.2 vs 11.9 +/- 6.4; ns3 were similar in the two groups. fertilization rate [73.3%va 75.8%; NS], mean number of grade I and 2 embryos [6.3 +/- 2.7 vs 6.9 +/- 3.9; NS], mean number of transferred embryos [1.9 +/- 0.7 vs 1.8 +/- 0,7; NS],implantation rate[13.3%vs 18.45%; ns] and clinical pregnancy rate per transfer [28.6%vs 31.1%;ns] did not differ statistically is she two groups. Twin and triplet pregnancies rates were also similar in the two groups [7.1%vs 9.3%; NS] and [3S%vs 3.1%; NS] respectively. Live birth rate [12,2%vs 20.7%; p<0.001] was significantly lower in GnRH antagonist group and miscarrage rate was significantly higher in this same group [42.8%vs 18.7%;p<0.001]. GnRH antagonist protocol is a short and simple protocol with a significant reduction in incidence of OHSS and amount of gonadotrophins. However. GnRH antagonist protocol provides a lower live birth rate and an increased risk of early pregnancy loss compared no the GnRH agonist long protocol. Further studies are necessary for more solid conclusions