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Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques.

A prospective, randomized, comparative, assessor-blind study was carried out in two centres to compare the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (u-hFSH HP; Metrodin HP), both administered s.c. in women undergoing ovarian stimulation for in-vitro fertilization including intracytoplasmic sperm injection (ICSI). A total of 235 patients started a long gonadotrophin-releasing hormone agonist protocol: 119 received r-hFSH and 114 received u-hFSH HP (150 IU/day) for the first 6 days. Two patients were excluded from the study because they mistakenly received the incorrect treatment combination. Human chorionic gonadotrophin (HCG; 10000 IU, s.c.) was administered once there was at least one follicle 18 mm in diameter and two others > or = 16 mm. In all, 119 (100%) and 102 (89%) of the patients respectively in the r-hFSH and u-hFSH HP groups achieved the criteria for HCG. The mean numbers (+/- SD) of oocytes recovered (the primary endpoint) were 12.2 +/- 5.5 and 7.6 +/- 4.4 in the r-hFSH and u-hFSH HP groups respectively (P < 0.0001). However, the number of FSH treatment days (11.0 +/- 1.6 versus 13.5 +/- 3.7) and the number of 75 IU ampoules (21.9 +/- 5.1 versus 31.9 +/- 13.4) used were significantly less (P < 0.0001) in the r-hFSH group than in the u-hFSH HP group. In patients treated using ICSI (63 patients in each group), no difference in oocyte maturation was observed. The mean numbers of embryos obtained were 8.1 +/- 4.2 and 4.7 +/- 3.5 (P < 0.0001), in favour of the r-hFSH group. In the majority of patients (96 and 99% respectively) only one or two embryos were replaced (mean 2.0 +/- 0.2 and 1.9 +/- 0.1 respectively) in the r-hFSH and u-hFSH HP groups. The clinical pregnancy rates per started cycle and per embryo transfer were 45 and 36%, and 48 and 47%, respectively in the r-hFSH and u-hFSH HP groups (not significant). There were six (5.1%) and two (1.7%) cases of ovarian hyperstimulation syndrome respectively. In conclusion, it was found that r-hFSH was more effective than u-hFSH at inducing multiple follicular development. However, the high rate of low ovarian response in the u-hFSH group compared with our general experience was unexpected. The availability of a gonadotrophin with less inter-batch variation would be beneficial for clinicians. r-hFSH seems to fulfil such a requirement.

Adolescent↗

A double-blind, randomized study to compare recombinant human follicle stimulating hormone (FSH; Gonal-F) with highly purified urinary FSH (Metrodin) HP) in women undergoing assisted reproductive techniques including intracytoplasmic sperm injection. The French Multicentre Trialists.

This prospective, double-blind, randomized, multicentre study compared the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F((R))) versus highly purified urinary FSH (u-hFSH HP; Metrodin((R)) HP) in women undergoing ovarian stimulation for in-vitro fertilization, including intracytoplasmic sperm injection. A total of 278 patients began a long gonadotrophin-releasing hormone agonist protocol, then 139 received r-hFSH and 139 u-hFSH HP, 150 IU/day administered s.c., for the first 6 days of treatment. On day 7, the dose was adjusted, if necessary, according to ovarian response. Human chorionic gonadotrophin (HCG, 10 000 IU, s.c.) was administered once there was more than one follicle 18 mm in diameter and two others >/=16 mm. Oocyte retrieval was performed 36-38 h after HCG injection: 128 patients (92%) receiving r-hFSH and 113 (81%) receiving u-hFSH HP had at least one oocyte retrieved. Among patients receiving r-hFSH, there was a significantly higher mean (+/- SD) number of oocytes retrieved (11.0 +/- 5.9 versus 8.8 +/- 4.8 with u-hFSH HP; P = 0. 002) and mean number of embryos obtained (5.1 +/- 3.7 versus 3.5 +/- 2.9 with u-hFSH HP; P = 0.0001). With r-hFSH, significantly fewer FSH treatment days (11.7 +/- 1.9 versus 14.5 +/- 3.3) and 75 IU ampoules (27.6 +/- 10.2 versus 40.7 +/- 13.6) were required than with u-hFSH HP (P = 0.0001). Embryo replacement on day 2-3 after oocyte retrieval resulted in 36 liveborn children in the Gonal-F((R)) group and 33 in the Metrodin HP((R)) group (not significant). There were seven cases (5.0%) of ovarian hyperstimulation syndrome in the r-hFSH group and three (2.2%), in the u-hFSH HP group (not significant). It is concluded that r-hFSH is more effective than u-hFSH in inducing multiple follicular development.

Adolescent↗

A method of short-term cryostorage and selection of viable sperm for use in the various assisted reproductive techniques.

The objective of this study was to determine if spermatozoa, following short-term cryostorage at 5 degrees C in Test-Yolk buffer (TYB; ZBL, Inc., Lexington, KY, USA), could be recovered and improved via the SpermPrep filtration method and to assess the possibly enhanced fertilizing capacity of the selected spermatozoa. Semen specimens from 20 men were collected, evaluated, diluted 1:1 (v/v) with TYB, divided into aliquots and cooled to 5 degrees C for 24 and 48 hr. Semen samples were assessed for volume, sperm count, percentage and grade of motility, percentage of morphologically normal spermatozoa and outcome of the sperm penetration assay (SPA). After storage, aliquots were rewarmed at 37 degrees C, centrifuged, and the pellet was resuspended in 1.0 ml of SpermPrep media (ZBL, Inc.). Following 15 min of incubation, the rewarmed spermatozoa were filtered via the SpermPrep I filtration column (ZBL, Inc.) and assessed accordingly. The results obtained in this study indicate that the short-term cryostorage procedure yielded spermatozoa of adequate qualitative characteristics when compared to the fresh spermatozoa. Furthermore, filtration of rewarmed specimens yielded spermatozoa of significantly higher qualitative characteristics and superior fertilizing capacity following a short-term cryostorage period in TYB when compared to fresh and rewarmed spermatozoa (p < 0.05). This method of short-term cryostorage in TYB and selection of superior spermatozoa via the SpermPrep filtration method could further enhance the fertilizing ability of patients who produce spermatozoa characterized by deficient capacitation, acrosome reaction and subsequent fertilization.

Cryopreservation↗

[Artificial reproductive techniques: comparison of embryo transfer on day two or day three].

OBJECTIVES: Due to the lack of adequate media which could support embryo in vitro development in early IVF procedure day 2 transfer has been a dominated procedure. However, day 3 transfers more physiological to in vivo conditions and may pre-select embryos with better prognosis. MATERIALS AND METHODS: A studied group was 131 infertile couples subjected to classical IVF or ICSI in proportion, and day 2 transfer was performed in 67 cycles, while day 3 transfer in 64 cycles. Average age of both groups was comparable--around 31 years of age. In all cycles the long protocol of stimulation was applied. For in vitro culture--MediCult (Denmark) medium was employed. RESULTS: There were no statistical differences in proportion of class A to B embryos in a group with day 2 transfer (respectively: 65.2% and 30.4%) and in a group with day 3 transfer (respectively: 63.5% and 30.8% for A and B embryos). Similar rates of pregnancies per cycle were obtained--25.4% and 25.0% respectively for day 2 and day 3 transfer. There were also no statistical differences in implantation rate per cycle (28% and 27% respectively). CONCLUSIONS: Performed analysis did not allow to indicate statistical significant differences in laboratory and clinical data for both studied groups. However, retrospective study does not exclude subjective criteria that could be applied to individual will of the patient regarding a day of transfer.

Adult↗

Efficacy of recombinant human follicle-stimulating hormone in improving oocyte quality in assisted reproductive techniques.

OBJECTIVE: To estimate the efficacy of recombinant human follicle-stimulating hormone (rFSH) versus highly purified urinary human FSH (uFSH) in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET). STUDY DESIGN: This prospective, randomized, quality of retrieved double-blind study compared uFSH with rFSH in IVF-ET rFSh cycles. A total of 254 cycles from 241 patients who attended the infertility clinic at Samsung Cheil Hospital from January to August 2001 were included in the study. With pituitary desensitization using gonadotropin-releasing hormone agonist and a short protocol, rFSH was administered in 131 cycles; uFSH was administered in 123 cycles. We analyzed ovarian response, oocyte quality, fertilization rate, embryo quality, pregnancy rate and live birth rate in the uFSH and rFSH groups. RESULTS: Total FSH dosage (1322.3 +/- 526.2 vs. 2124.4 +/- 881.9 i.u.) and dosage per retrieved oocyte (90.6 +/- 36.0 vs. 138.0 +/- 57.2 i.u.) were significantly lower in the rFSH group than those in the uFSH group (P < .001). The proportion of good-quality oocytes (grade 1 and 2) was higher in the rFSH group (68.2% vs. 64.8%, P = .024). Moreover, the proportion of atretic oocytes (grade 5) was lower in the rFSH group (7.5% vs. 10.3%, P = .002). The fertilization rate, quality of transferred embryos, clinical pregnancy rate and live birth rate were not significantly differ between the 2 groups. CONCLUSION: In women undergoing COH, rFSH revealed more efficient ovarian response and better quality of oocytes than did uFSH.

Adult↗

[Medico-administrative aspects of medically assisted reproduction techniques].

Artificial procreation techniques raise many ethical questions. The National Consultative Ethics Committee has pronounced on two occasions on this subject. Apart from ethical considerations, the rapid development of various techniques has required regulations aimed at ensuring the quality of the medical activities performed. The decree of April 8, 1988 concerning medically assisted procreation limits the practice of these activities to hospitals and medical biology laboratories. These regulations do not apply to fundamental questions which fall in the realm of legislation. A bill has already been drafted; if it passes it might provide a few guiding marks on this subject for practitioners and for society as a whole.

Ethics, Medical↗

[Cryopreservation of embryos--used for treatment of infertility by means of assisted reproductive techniques (ART)].

Freezing of the human embryos has been routinely used in the world for over 10 years in the treatment of infertility by the ART. Excessive fertilized oocytes and embryos can be frozen and preserved in the temperature of liquid nitrogen. The risk of multiple pregnancies is reduced and enhancement of pregnancy rates can be obtained owing to cryopreservation. The author presents theoretical principles of embryo freezing by slow cooling with 1, 2 propanediol and saccharose as a cryoprotectant.

Cryopreservation↗

Hysteroscopic septum resection in patients with recurrent abortions or infertility.

Fifty-seven patients who underwent hysteroscopic septum resection between January 1991 and December 1996 were studied; nine patients presented with recurrent abortions, 46 with infertility (26 primary and 20 secondary), one with dysmenorrhoea and one with an asymptomatic complete septum. Their reproductive history included 78 pregnancies: 69 (88.4%) abortions, two (2.6%) ectopics, two (2.6%) preterm deliveries and five (6.4%) term deliveries. In patients with infertility, the incidence of unexplained infertility was 19.6% and the incidence of endometriosis was 26.1%. After hysteroscopic septum resection, 42 patients were interested in pregnancy. All patients with recurrent abortions conceived spontaneously. Twenty-one (63.6%) infertile patients achieved a pregnancy, 13 (61.9%) of them after treatment with various assisted reproduction techniques. The reproductive outcome after septum resection yielded 44 pregnancies, including three sets of twins and one set of triplets reduced to twins: 11 (25%) abortions, one (2.3%) ectopic pregnancy, two (4.5%) preterm deliveries (both twins), 28 (63.7%) term deliveries and two (4.5%) as-yet ongoing pregnancies. It seems that the hysteroscopic treatment of uterine septum has a beneficial effect on pregnancy outcome. A septate uterus does not seem to be an infertility factor. The achievement of pregnancy is normal in patients with recurrent abortions, while the chances of conception in patients with infertility seem to be similar to those for the general infertile population.

Abortion, Habitual↗

Use of reproductive technology to estimate variances and predict effects of gene interactions.

Advanced reproductive techniques are creating the large numbers of close relatives needed to study gene interactions. Identical triplets, a set of 26 full sisters, a family of 4215 three-quarter sisters (same sire and maternal grandsire), a family of 76,698 half sisters, and 1.6 million granddaughters of Round Oak Rag Apple Elevation now have lactation records. Similarity of closest relatives might be explained by similar nonadditive as well as additive genetic merit. The 23,015 families of full sisters with mean family size of 3 provide nearly as much information about dominance variation as do the 55,779 families of three-quarter sisters with mean family size of 13; the 79 families of clones provide little information by comparison. Hypothetically, REML analysis of all US Holstein data could provide estimates of dominance and additive x additive variance with standard errors approximately 1% of phenotypic variance, but estimates of any higher order interactions would have standard errors greater than 10%. The tilde-hat approximation proved to be incompatible with animal models but was used for sire-maternal grandsire analysis of 765,868 first lactation records. Dominance variance was estimated as 3.5% of phenotypic variance for milk and 3.3% for fat with standard error of 4.2%. With constant data set size, variances are estimated most precisely if family sizes equal 1 plus ratio of within-family to between-family variance. An animal model evaluation including dominance relationships for 581,670 animals was computed, but gene interactions from distant ancestor pairs were ignored. Mating advice and improved additive predictions, especially for clones, could be obtained by including dominance in models.

Animals↗

[Diagnosis and treatment of the male factor in the age of intracytoplasmic sperm injection].

Currently, we are witnesses of the Assisted Reproductive techniques; advances reproductive goals have been reached with the Intracytoplasmic Sperm Injection (ICSI) in patients with male factor. However, micromanipulation techniques allowed the reproductive solution without an etiologic and/or physiopathologic diagnosis. The andrologic workup of the dynamic and functional sperm characteristics with the endocrine and urologic evaluation should be performed into the infertility management.

Humans↗

Medically assisted reproduction in the presence of chronic viral diseases.

Teams practising medically assisted reproduction techniques try to avoid viruses as much as possible. Attitudes towards chronic carriers of viruses are rapidly changing, especially for human immunodeficiency virus (HIV) patients. We focus our attention on the legitimacy of systematic screening before assisted reproductive techniques and the need for specialized approaches including an adapted laboratory for viral hazards as well as the need for a multidisciplinary team. Specificities of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV) carriers and the hypothesis of a reduced fertility potential are discussed. Are male HIV carriers a new indication for assisted reproductive techniques in order to prevent virus transmission? It is largely proven that sperm gradient preparation techniques efficiently decrease viral loads and therefore have a protective effect on contamination risk during assisted reproductive techniques. Although a few thousand assisted reproductive technique cycles were performed in the world for this indication without contamination, it is still too early to demonstrate that this technology is fully safe. Two examples of contaminations during insemination are examined. Many questions remain unresolved, such as the lack of standardized techniques for semen preparation or virus detection or the relative merits of intrauterine insemination or ICSI to prevent HIV contamination during assisted reproductive techniques. The authors plead for well-structured, separate programmes of care linked to research objectives.

Acquired Immunodeficiency Syndrome↗