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The use of intracytoplasmic sperm injection with electroejaculates from anejaculatory men.

Electroejaculation has been successfully used for sperm procurement in anejaculatory men desiring fertility. However, electroejaculates typically have normal sperm numbers but poor motility, morphology, and functional deficiencies. Here we report the pregnancy outcome of a series of couples undergoing combined electroejaculation and in-vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). In all, 13 couples underwent a total of 18 cycles. The aetiologies of anejaculation included history of retroperitoneal lymph node dissection for testicular cancers, spinal cord injury and psychogenic causes. ICSI was performed on 192 oocytes, resulting in a fertilization rate of 75.5%. A total of 15 embryo transfers were performed using a total of 51 embryos. Clinical pregnancy rate, as defined by positive fetal heart rate(s) using vaginal sonography, was 55.6% per retrieval; implantation rate was 33.3% per embryo. These rates appear to be similar to those obtained in standard IVF for non-male factor infertility, or ICSI for male factor infertility. The use of ICSI for electroejaculates undoubtedly provides these couples with the highest chance of pregnancy.

Ejaculation↗

GnRH antagonist improved blastocyst quality and pregnancy outcome after multiple failures of IVF/ICSI-ET with a GnRH agonist protocol.

BACKGROUND: To determine the efficacy of a gonadotrophin-releasing hormone (GnRH) antagonist, cetrorelix, in improving the quality of embryos and pregnancy outcome, we performed a study in patients with a history of multiple failures of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles with a GnRH agonist (GnRHa) long protocol. METHODS: Forty women with no live births after conventional IVF or ICSI embryo transfer (ET) and subsequent blastocyst transfer (BT) with a GnRHa long protocol entered this study. The treatment protocol consisted of a daily dose of clomiphene citrate 100 mg for 5 days and gonadotrophin injections daily from cycle day 4 onward. Cetrorelix, 0.25 mg/day, was started when the leading follicle reached 14 mm. Induction of ovulation was triggered with human chorionic gonadotrophin (HCG) (N = 36) or GnRHa (N = 4). It was possible to perform BT in 38 patients. RESULTS: Comparison of the results with the results for BT with the previous GnRHa protocol showed no significant differences in number of oocytes retrieved or the zygote- and blastocyst-development rate. With the cetrorelix protocol, however, number of patients whose embryos had developed to at least one expanded blastocyst on day 5 was significantly higher than with the GnRHa protocol (25 vs. 9) (p < 0.001), and 16 of the women became pregnant (42.1%), with 7 delivering 9 infants, 4 ending in abortion (25%), and 5 in progressing. CONCLUSIONS: The use of a GnRH antagonist in controlled ovarian hyperstimulation improves the outcome of pregnancy of patients with a history of multiple failure of IVF/ICSI-ET in a GnRHa protocol, most likely due to improvement of the quality of the blastocysts generated.

Adult↗

ICSI outcome in patients of 40 years age and over: a retrospective analysis.

OBJECTIVE: To report and analyse our experience with ICSI treatment in infertile women >/=40 years of age, with the intention of contributing to current debates on the effect of aging on the reproductive potential. STUDY DESIGN: 107 infertile couples in which the female partner was aged >/=40 years and who received ICSI treatment between January 1996 and December 1998. RESULTS: A total of 107 women underwent 171 treatment cycles during this period. Of 171 cycles initiated 33 were cancelled (cancellation rate=19.3%). In this way, 17 women did not have embryo transfer at all, while 90 patients had 138 cycles with oocyte retrieval and successful embryo transfer, with a mean number of embryos per transfer 2.36. Sixteen pregnancies occurred and eight of them ended in spontaneous abortion. The implantation rate was 4.9%, the pregnancy rate per initiated cycle was 9.35% and per transfer cycle 11.59%. The miscarriage rate was 50%. Moreover, 12 patients had supernumerary embryos, that were cryopreserved and transferred in 17 thawing cycles and resulted in two pregnancies ending in abortion. All pregnancies occurred when three embryos were available, except in two cases with two available embryos. The great majority of the total pregnancies (16 of 18) resulting in women aged between 40 and 42 years. CONCLUSION: Our data show that women 40 and older with existing ovarian function may benefit from ICSI treatment, even when the indication for treatment is male factor infertility. Supernumerary embryos, that are cryopreserved and transferred in subsequent cycles can improve the overall pregnancy rates per oocyte retrieval, although these women should be aware of the very high risk of miscarriage.

Abortion, Spontaneous↗

The potential use of maturation in vitro of human oocytes in low responder patients.

PURPOSE: To assess whether maturation in vitro of human oocytes (MIVHO) could be an alternative treatment in low responders to ovarian stimulation for in vitro fertilization (IVF). METHODS: Prospective case-control study. Spontaneously ovulatory women who volunteered were included in our program of MIVHO at the Instituto Valenciano de Infertilidad. Rates of oocyte retrieval, in vitro maturation, fertilization, and development up to the blastocyst stage were studied. RESULTS: A significantly increased rate of oocyte retrieval was found when the pickup was performed before follicular selection. No differences were found when MIVHO was used in a low responder patient with an ovarian content of early antral follicles > 5 as compared to normal responders. CONCLUSIONS: MIVHO could be a successful choice in low responder patients with an acceptable number of early antral follicles. Oocyte retrieval should be performed before follicular selection in order to obtain more oocytes.

Adult↗

Neurological sequelae in twins born after assisted conception: controlled national cohort study.

OBJECTIVE: To compare neurological sequelae in twins born after assisted conception with singletons after assisted conception and naturally conceived twins and to assess neurological sequelae in children conceived after in vitro fertilisation (IVF) compared with intracytoplasmic sperm injection (ICSI). DESIGN: Controlled, national register based, cohort study. PARTICIPANTS: Twins (n = 3393) and singletons (n = 5130) conceived by using assisted reproductive technologies and naturally conceived twins (n = 10 239) born in Denmark between 1995 and 2000. The children's age at time of follow up was 2-7 years. DATA SOURCES: Children were identified by cross linkage of the national medical birth registry and the national registry for in vitro fertilisation. Neurological and psychiatric diagnoses were retrieved from the national patients' registry and the Danish psychiatric central registry. MAIN OUTCOME MEASURES: Neurological sequelae, defined as cerebral palsy, mental retardation, severe mental developmental disturbances, and retarded psychomotor development. Further we made separate analyses on the specific cerebral palsy diagnosis. RESULTS: The crude prevalence rates per 1000 of neurological sequelae in twins and singletons after assisted conception and in naturally conceived twins were 8.8, 8.2, and 9.6, and of cerebral palsy 3.2, 2.5, and 4.0, respectively. In twins after assisted conception compared with control twins, the odds ratios of neurological sequelae and specifically of cerebral palsy, adjusted for child sex and year of birth, were 0.9 (95% confidence interval 0.6 to 1.4) and 0.8 (0.4 to 1.6), respectively. The corresponding odds ratios for twins after assisted conception compared with singletons after assisted conception were 1.1 (0.7 to 1.7) for neurological sequelae and 1.3 (0.6 to 2.9) for cerebral palsy. The odds ratio of neurological sequelae in children conceived by ICSI was 0.9 (0.5 to 1.7) nu children conceived by IVF. CONCLUSIONS: Twins from assisted conception have a similar risk of neurological sequelae as their naturally conceived peers and singletons from assisted conception. Children born after ICSI have the same risk of neurological sequelae as children born after IVF.

Cohort Studies↗

Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH. On behalf of The Feronia and Apis study group.

This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F) with highly purified urinary human FSH (uhFSH, Metrodin HP) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F or Metrodin HP, at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F and Metrodin HP groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F than with Metrodin HP (11.6 +/- 1.9 days versus 12. 4 +/- 2.7 days; P < 0.0001) and significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/- 5.1, P < 0.0002). There were, however, significantly more follicles > or =10 mm in diameter with Gonal-F (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P < 0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F had a higher pregnancy rate per cycle than patients given Metrodin HP (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F and Metrodin HP patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F is clearly more effective than Metrodin HP in inducing multifollicular development.

Adult↗

Ureaplasma urealyticum and Mycoplasma hominis detected by the polymerase chain reaction in the cervices of women undergoing in vitro fertilization: prevalence and consequences.

PURPOSE: The prevalence of Ureaplasma urealyticum and Mycoplasma hominis in the endocervix at the time of oocyte collection in women undergoing in vitro fertilization (IVF) was examined using the polymerase chain reaction (PCR). METHODS: All women were treated with tetracycline following sample collection. RESULTS: U. urealyticum was identified in 56 (17.2%) of 326 women while M. hominis was present in only 5 (2.1%) of 235 women. U. urealyticum was detected at a higher frequency (P = 0.01) in those women whose IVF cycle failed prior to embryo transfer. This organism was present in 8 of 19 (42.1%) women with either no fertilization or no embryo transfer, 19 of 148 (12.8%) who had no evidence of pregnancy following embryo transfer, 6 of 30 (20.0%) who had only a transient (biochemical) pregnancy, 5 of 14 (35.7%) with a spontaneous abortion, and 18 of 115 (15.6%) with a term birth. Of the eight women with U. urealyticum who had no embryos transferred, male factor was the cause of infertility in five cases, two women had tubal occlusions while in one woman the diagnosis was idiopathic. Therefore, poor sperm quality, and not a U. urealyticum infection, might explain the failure of most of these cases to proceed to the stage of embryo transfer. Analysis of all patients revealed no association between male factor infertility and U. urealyticum in the cervix. CONCLUSIONS: U. urealyticum, but not M. hominis, is present in the cervices of many culture-negative women. Its presence, however, does not influence IVF outcome subsequent to embryo transfer in women treated with tetracycline after oocyte retrieval.

Adult↗

Basal 17beta-estradiol did not correlate with ovarian response and in vitro fertilization treatment outcome.

OBJECTIVE: To verify the correlation of basal 17beta-E(2) with ovarian response to stimulation and outcome of in vitro fertilization (IVF). DESIGN: Retrospective observational study. SETTING: The Assisted Conception Unit, University College London Hospitals. PATIENT(S): Three hundred five women undergoing IVF and IVF with intracytoplasmic sperm injection. INTERVENTION(S): Basal follicle-stimulating hormone (FSH) and 17beta-E(2) were assessed. The cutoff level for day 2 E(2) established was 250 pmol/L. Each patient was noted for below (group A) or above (group B) the cutoff point according to her basal E(2) level. MAIN OUTCOME MEASURE(S): Basal E(2), age, duration of infertility, cycle day 2 FSH, number of ampules of gonadotropin used, number of days of stimulation, number of retrieved oocytes, fertilization rate, number of embryos transferred, number of cycles with embryo freezing, cancellation rate, clinical pregnancy rate, and implantation rate were compared between the two groups. RESULT(S): No differences were found between group A and group B in the number of oocytes retrieved (8.8 +/- 4.2 vs. 9.3 +/- 4.8), embryos transferred (2.5 +/- 0.8 vs. 2.7 +/- 0.7), cancellation (9.1% vs. 6.9%), pregnancy (24.8% vs. 30%), and implantation rate (12.3% vs. 15.6%). Correlation coefficient and coefficient of determination showed no significant correlation between basal E(2) and the number of oocytes retrieved, age, and basal FSH. CONCLUSION(S): In our study population, basal E(2) was not a sensitive predictor of ovarian response to stimulation and did not correlate with IVF outcome.

Adult↗

GnRH agonist versus GnRH antagonist in poor ovarian responders: a meta-analysis.

The aim of this meta-analysis was to compare the efficacy of gonadotrophin antagonist (GnRH-ant) versus GnRH agonist (GnRHa) as coadjuvant therapy for ovarian stimulation in poor ovarian responders in IVF/intracytoplasmic sperm injection cycles. Search strategies included on-line surveys of databases such as MEDLINE , EMBASE and others. A fixed effects model was used for odds ratio (OR) and effect size (weighted mean difference, WMD). Six trials fulfilled the inclusion criteria (randomized controlled trials). There was no difference between GnRH-ant and GnRHa (long and flare-up protocols) with respect to cycle cancellation rate, number of mature oocytes and clinical pregnancy rate per cycle initiated, per oocyte retrieval and per embryo transfer. When the meta-analysis was applied to the two trials that had used GnRH-ant versus long protocols of GnRHa, a significantly higher number of retrieved oocytes was observed in the GnRH-ant protocols [P=0.018; WMD: 1.12 (0.18, 2.05)]. However, when the meta-analysis was applied to the four trials that had used GnRH-ant versus flare-up protocols, a significantly higher number of retrieved oocytes (P=0.032; WMD: -0.51, 95% CI -0.99, -0.04) was observed in the GnRHa protocols. Nevertheless, additional randomized controlled trials with better planning are needed to confirm these results.

Drug Administration Schedule↗

Impact of metformin therapy on ovarian stimulation and outcome in 'coasted' patients with polycystic ovary syndrome undergoing in-vitro fertilization.

This study was designed to determine if metformin therapy improves ovarian stimulation and IVF outcomes in coasted patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). A retrospective data analysis was performed on women with clomiphene citrate-resistant PCOS treated with or without metformin, who underwent 72 cycles of IVF-embryo transfer with intracytoplasmic sperm injection (ICSI). In 59 cycles, patients were coasted to allow oestradiol concentrations to drop before human chorionic gonadotrophin administration. In patients undergoing coasting, the outcome of IVF with ICSI was compared in those who were treated and untreated. In patients treated with metformin, follicular fluid concentrations of testosterone and insulin were significantly lower (60.5 +/- 5 versus 79.1 +/- 6 ng/dl; P < 0.05 and 18 +/- 2.5 versus 22 +/- 2.4 micro IU/ml; P < 0.05 respectively), and the mean number of oocytes retrieved (22.3 +/- 2.4 versus 19.7 +/- 1.6) did not differ. The metformin-treated group showed an increase in the mean number of mature oocytes, oocytes fertilized and cleaving embryos (4-cell or greater by 72 h). However, in the group of patients undergoing coasting, maximum oestradiol concentrations and number of days of coasting were all lower in the metformin-treated group with increased clinical pregnancy rates (71 versus 30%, P < 0.05). Therefore, metformin use appears beneficial in improving IVF outcomes in clomiphene citrate-resistant PCOS patients.

Adult↗

Comparison of microscopic epididymal sperm aspiration and intracytoplasmic sperm injection/in-vitro fertilization with repeat microscopic reconstruction following vasectomy: is second attempt vas reversal worth the effort?

Since 1986, we have performed microscopic reconstruction in 18 men following failed microscopic vasectomy reversal. Between 1994 and 1996, nine couples have undergone microscopic epididymal sperm aspiration (MESA)/ intracytoplasmic sperm injection (ICSI) treatment for male infertility due either to congenital absence of the vas deferens (CAVD) or inoperable excurrent duct obstruction. We compared the cost efficiency of repeat vasectomy reversal to that for MESA combined with ICSI/in-vitro fertilization (ICSI/IVF). The cost of male partner procedures (vasectomy reversal, MESA) was based on physician and hospital charges, while the cost of ICSI/IVF included preparation of the female partner (medications and physician charges) and procedures (physician and hospital charges including oocyte retrieval, micromanipulation, and embryo transfer). Our cost examination does not include charges related to follow-up visits, prenatal monitoring, complications of pregnancy (i.e. miscarriage) or delivery in either group. Overall patency and pregnancy rates in the repeat vasectomy reversal group were 78 and 44% respectively. The cost per delivered baby (including multiple metachronos deliveries per couple) was $14892. Fertilization of oocytes has been achieved in 37/72 (51%) and pregnancies have occurred in 6/9 (67%) attempts and 5/9 (56%) report delivery. The average cost per pregnancy was $25637 and the average cost per delivered baby (or ongoing pregnancy) was $35570. The cost per delivery by MESA/ ICSI/IVF is 2.4 times the charges per delivery obtained through repeat vasectomy repair. Couples attempting to overcome infertility caused by vasal obstruction should be informed that vas reconstruction remains a cost effective means of re-establishing fertility even in men who have previously failed vasectomy reversal.

Cost-Benefit Analysis↗

[Twenty years of in vitro fertilization: realization and questions for the future].

IVF is a well-established procedure for the treatment of longstanding infertility due to tubal disease, endometriosis, unexplained infertility or certain types of infertility involving a male factor. IVF can also be applied to couples requiring oocyte donation. Conventional IVF involves several related procedures: patient selection, ovarian stimulation, oocyte retrieval, semen preparation, insemination of cumulus-oocyte complexes, assessment of fertilization, assessment of embryo cleavage, replacement to the uterus of mostly two or three embryos, cryopreservation of excess embryos and establishment of pregnancy. GIFT and ZIFT are related techniques, suitable in couples with at least one healthy Fallopian tube. Conventional IVF is a potentially successful procedure in patients with tubal and unexplained infertility. However, fertilization may fail in couples with certain forms of andrological infertility, especially those in which sperm function is severely deficient. Techniques of assisted fertilization--partial zona dissection (PZD) and subzonal insemination (SUZI)--have been used with limited success to treat couples with severe andrological infertility who could not be helped by conventional IVF. ICSI--the injection of a single spermatozoon into the cytoplasm of a fertilizable metaphase II oocyte--has proved to be more efficient than PZD and SUZI for the alleviation of severe male-factor infertility. Nowadays ICSI can be considered as an infertility treatment, providing similar results in male infertility as conventional IVF in female-factor or idiopathic infertility. The ICSI treatment involves several related steps: selection of patients for ICSI, ovarian stimulation and oocyte handling, evaluation and preparation of spermatozoa, the ICSI procedure itself, oocyte damage and pronucleus formation after ICSI, embryo development and replacement and cryopreservation of excess embryos. The audit of IVF and ICSI results is hampered by the way these data are registered in different countries and different centers. A correct and reliable analysis is possible in the United Kingdom; the UK data bank was used to study the factors influencing the outcome of IVF--especially the female age has a determining role. Infertility treatments have induced a sharp increase in the number of multiple pregnancies. Reducing the number of multiple gestations should be considered as a future major challenge for all infertility centers. Since its introduction in 1991 questions have been raised concerning the safety of ICSI, a novel and efficient assisted fertilization procedure. A careful follow-up of the ICSI pregnancies and children is therefore indicated. At the VUB this prospective follow-up of genetic counseling, the possibility of prenatal diagnosis, the problems during pregnancy, the occurrence of (major) congenital malformations as well as a further medical and psychomotor follow-up. The results of 1437 fetal karyotypes indicate that in comparison with a control group there is after ICSI a slight but significant increase of sex chromosomal aneuploidies and de-novo structural aberrations. The percentage of ICSI children (n = 2840) with major congenital malformations was similar to the malformation rate in children from conventional IVF (n = 2955) or natural conception. This prospective follow-up study should be continued much longer--if possible until adulthood to assess the fertility of these children.

Female↗

Placental protein 14 concentrations in circulation related to hormonal parameters and reproductive outcome in women undergoing IVF/ICSI.

Serum concentrations of placental protein 14 (PP14), steroids and gonadotrophins were related to the outcome of IVF/intracytoplasmic sperm injection in 195 normogonadotrophic women subjected to the long protocol gonadotrophin-releasing hormone agonist (GnRHa; buserelin) pituitary down-regulation protocol and gonadotrophin stimulation (HMG or rFSH). Pituitary down-regulation was initiated on cycle day 21 and the patients were randomized to either intranasal or s.c. administration of buserelin. After 14 days of down-regulation, the patients were randomized on stimulation day 1 (S1) to ovarian stimulation with 225 IU per day of either human menopausal gonadotrophin (HMG) or recombinant FSH (rFSH) for a fixed period of 7 days. The daily gonadotrophin dose was adjusted on the following day according to ovarian response. Patient's blood was sampled for PP14 and hormone analysis on cycle days 21, S1, S8 and on the day of oocyte retrieval. Mean concentrations of PP14 on day 21 of the cycle were significantly lower in conception than in non-conception cycles, whereas progesterone and oestradiol were similar in conception and non-conception cycles. PP14 concentrations on the first day of stimulation and at oocyte retrieval were significantly higher in conception than in non-conception cycles, whereas concentrations after 8 days of stimulation were similar. Neither mode of GnRHa administration nor type of gonadotrophin significantly influenced PP14 concentrations throughout ovarian stimulation. Circulating PP14 is thus an important physiological signal of the fertility status of the individual in the cycle antecedent to and during ovarian stimulation. Measuring mid-luteal serum PP14 may offer a clinical test helping to decide if infertility treatment should be initiated in the subsequent cycle.

Adult↗

Impact of ACTH administration on the oviductal sperm reservoir in sows: the local endocrine environment and distribution of spermatozoa.

The objective of the study was to investigate if short-term stress in sows (simulated by injections of synthetic adrenocorticotrophic hormone (ACTH)) during standing oestrus had a negative effect on the local environment in the utero-tubal junction (UTJ) and isthmus and the distribution of spermatozoa in these segments. Fourteen sows were monitored for ovulation using ultrasonography in two consecutive oestruses. The sows were fitted with jugular catheters and, from onset of the second oestrus, blood samples were collected every second hour. In the 2nd oestrus, seven sows were given ACTH every second hour, from the onset of standing oestrus until the sow ovulated (ACTH-group), whereas the other seven sows remained as controls (C-group) and were given NaCl solution. The sows were artificially inseminated 16-18 h before expected ovulation. Six hours after ovulation the sows were anaesthetised, and blood samples were repeatedly taken from veins draining the uterus and the UTJ-isthmus, respectively. This oviduct was thereafter removed and divided in four adjacent sections consisting of: (i) the UTJ, (ii) the first, and (iii) the second isthmus segment prior to (iv), the ampullary-isthmic junction (AIJ) and the ampulla. The three first-mentioned segments were flushed to retrieve spermatozoa, whereas the last one was flushed to collect oocytes/ova. The number of spermatozoa attached to the zona pellucida was counted. The concentrations of cortisol in jugular blood of the ACTH-group sows during the time of ACTH-injections were significantly higher than of the C-group sows (p<0.05), as were the levels of progesterone (p<0.001). Progesterone and cortisol concentrations measured in the blood samples draining the UTJ-isthmic region 6 h after ovulation did not significantly differ between the groups, but the C-group displayed significantly higher concentrations of progesterone in the UTJ-isthmic region compared with the levels measured in parallel samples taken of jugular blood (p<0.01). The C-group, but not the ACTH-group, also displayed a significant elevation in progesterone concentration 6h after ovulation compared with the basal levels before ovulation (p<0.01). Numbers of retrieved spermatozoa were not significantly different between the C-group and the ACTH-group. However, there was a tendency for a larger number of spermatozoa among sows in the ACTH-group, especially in the isthmic segment adjacent to the AIJ. In conclusion, simulated stress induced by injections of ACTH during standing oestrus results in elevated concentrations of progesterone before ovulation and may interfere with the rise of progesterone after ovulation. However, ACTH-injections appeared to augment transport of spermatozoa through the female genital tract of pigs.

Adrenocorticotropic Hormone↗

Measurement of perifollicular blood flow of the dominant preovulatory follicle using three-dimensional power Doppler.

OBJECTIVE: To establish whether we might predict the outcome of unstimulated in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles with quantitative indices of perifollicular blood flow assessed with three-dimensional (3D) reconstruction of power Doppler images. METHODS: This prospective study included an analysis of 52 unstimulated cycles. Color and power Doppler ultrasound examinations of a single dominant preovulatory follicle were performed on the day of oocyte pick-up. With 3D reconstruction and processing, quantitative indices were obtained i.e. the percentage of volume showing a flow signal (VFS) inside a 5-mm capsule of perifollicular tissue and the percentage of VFS of each of the three largest vessels in this capsule. These indices as well as pulsed Doppler indices were compared between the groups of cycles with different outcomes using a one-way ANOVA test. RESULTS: In nine cycles no oocyte was retrieved (Group A), in seven cycles no fertilization occurred (Group B) and in 30 cycles no implantation occurred (Group C). Six cycles resulted in pregnancy (Group D). There were no statistically significant differences in pulsed and power Doppler indices between these groups. However, the percentage of VFS in the capsule was higher than average in cycles with implantation (19.22 +/- 16.82 vs. 12.42 +/- 8.89, NS) and the percentage of VFS in the main vessel exhibited lower than average values in cycles with implantation (20.66 +/- 10.05 vs. 39.84 +/- 20.15), but only reached borderline statistical significance (F = 2.457, P = 0.074). CONCLUSION: It can be hypothesized that the follicles containing oocytes able to produce a pregnancy have a distinctive and more uniform perifollicular vascular network.

Adult↗

Comparison of GnRH agonists and antagonists in assisted reproduction cycles of patients at high risk of ovarian hyperstimulation syndrome.

BACKGROUND: During IVF or ICSI cycles, ovarian hyperstimulation syndrome (OHSS) is a major problem. The aim of this prospective, multicentre, comparative study (using historical controls) was to assess the efficacy of a GnRH antagonist protocol in preventing OHSS in selected patients who had experienced OHSS or had been at risk of OHSS in their previous IVF/ICSI attempt. METHODS AND RESULTS: Patients underwent a new cycle where the same gonadotrophin protocol was used [same dose of recombinant FSH (rFSH)] but a different protocol was used for pituitary desensitization: cetrorelix 0.25 mg multiple-dose antagonist instead of GnRH agonist long protocol. Cetrorelix 0.25 mg was administered daily, starting when the leading follicle reached a diameter of 14 mm. In other words, rFSH was administered in the new cycle according to the dosage and the step-up or step-down modalities used during the previous cycle, independently of ultrasound findings and serum estradiol (E(2)) levels. Eighty-seven patients entered the study. Out of the 87 cycles involving GnRH agonists, 49 (56.3%) were cancelled and out of the 87 involving GnRH antagonists 28 (32.2%) were cancelled [McNemar's test; 95% confidence interval (CI) -35.8% to -11.2%; P < 0.001]. After GnRH agonist cycles, we recorded 24 cases of OHSS (18 moderate and six severe; 27.6%), whereas after the GnRH antagonist cycles there were 10 cases of OHSS (nine moderate and one severe; 11.5%) (95% CI-26.4% to -5.7%; P = 0.006). There was a statistically significant reduction in the total number of follicles with a diameter >10 mm (Wilcoxon's test; Z = 6.1; P < 0.001) and of E(2) levels on the day of HCG administration (2538 versus 4322.4 pg/ml; P < 0.001) in the GnRH antagonist cycles versus GnRH agonist cycles. Twenty-nine patients had an embryo transfer in the first cycle (76.3% of oocyte retrievals) and 57 in the cycle using GnRH antagonist (96.6%). This 20.3% difference was also significant (Z-test; 95% CI 6.8-36.0%; P = 0.003). After the antagonist cycles, 18 pregnancies (20.7 per initiated cycle; 31.6% per embryo transfer) were obtained. CONCLUSIONS: Although this study presents some limitations owing to the use of historical controls, our data show a favourable effect of GnRH antagonists in reducing the incidence of OHSS and the number of assisted fertilization cycles cancelled because of the risk of OHSS in high responder patients. As a consequence, GnRH antagonist plus gonadotrophin administration could also increase the percentage of oocyte retrievals and embryo transfers in this high risk group of patients.

Adult↗

[Preimplantation genetic diagnosis for beta-thalassemia using whole genome amplification].

OBJECTIVE: To achieve pregnancy with unaffected embryo using in vitro fertilization and embryo transfer (IVF-ET) and preimplantation genetic diagnosis(PGD) for the couples at risk of having children with beta-thalassemia. METHODS: A couple carrying different thalassemia mutations of codon 41/42 and codon IVS2 position 654 received standard IVF treatment and intracytoplasmic sperm injection, embryo biopsy, single cell polymerase chain reaction and DNA analyses, and only the unaffected or carrier embryos were transferred to uterus. Pregnancy confirmation, and prenatal diagnosis were done at 20 week's gestation. RESULTS: A total of 13 embryos were analyzed in the IVF cycle. PGD indicated that 2 were normal 18.1 , 3 were affected 27.3 , and 6 were carriers 54.5 ; diagnosis was not possible in 2. Three embryos were transferred to uterus on the third day after oocyte retrieval. Ultrasonography showed twin pregnancy with one blighted ovum. The prenatal diagnoses revealed that both fetuses were unaffected, one normal baby and one carrier were born. CONCLUSION: These studies represent the successful application of PGD for beta-thalassemia in China.

Adult↗

Treatment versus no treatment of transient hyperprolactinemia in patients undergoing intracytoplasmic sperm injection programs.

The aim of our study was to investigate the effect of increased plasma prolactin levels on oocyte and fertilization rate in patients undergoing in vitro fertilization (IVF) intracytoplasmic sperm injection (ICSI) treatment. We identified 135 patients with transient or borderline hyperprolactinemia, measured in the mid and late follicular phase and in the mid-luteal phase of the cycle before ovarian stimulation. The patients were assigned to either the no treatment group (76 patients) or the treatment group (59 patients). The treated group underwent treatment with cabergoline or bromocriptine before ovarian stimulation, until there was a decrease of plasma prolactin levels, and the therapy was continued also during the ICSI programme. Both groups received a gonadotropin-releasing hormone (GnRH) agonist and were subsequently stimulated with follicle-stimulating hormone (FSH) up to the day of human chorionic gonadotropin (hCG) administration. The untreated group needed a significantly lower number of FSH ampoules than the treated group to reach the day of hCG administration (38.1 +/- 18.2 versus 43.9 +/- 28.5; p < 0.05). No correlation was found between the two groups on the peak estradiol level achieved, the progesterone level at hCG administration and the numbers of oocytes retrieved. The number of oocytes with superior morphology (87.9% versus 80.4%; p < 0.05), the fertilization rate (70.8 +/- 28.0 versus 60.8 +/- 28.5; p < 0.03), and the mean number of embryos transferred (3.6 +/- 1.6 versus 3.2 +/- 1.5; p < 0.05) were significantly higher in the patients whose hyperprolactinemia was left untreated. In conclusion, we found that transient hyperprolactinemia is positively associated with ICSI outcome, in particularly with oocyte quality and fertilization rate.

Adult↗