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Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques.

BACKGROUND: This study analyses the prevalence of karyotype changes and Yq11 microdeletions among couples referred for assisted reproduction techniques. METHODS: Prior to receiving either IVF or ICSI treatment, each partner of 2078 infertile couples was screened for karyotype changes by GTG-banding technique on peripheral lymphocytes. No subject presented with obvious phenotype of chromosomal rearrangement. All the oligo/azoospermic men with normal karyotype were further investigated by PCR for Yq11 microdeletions. RESULTS: Eighty-two out of 2078 couples (3.95%) had one partner carrying a chromosomal change, and 10 out of 202 (4.95%) men showed Yq11 microdeletions. The chromosomal rearrangements were 44 (2.1%) translocations, 23 (1.1%) gonosomal mosaics, six (0.3%) 47,XXY, five (0.24%) marker chromosomes, three (0.14%) inversions and one (0.05%) duplication. Frequency of anomalies in men and women were similar: 42 and 40 cases respectively. CONCLUSIONS: Partners of infertile couples requiring IVF or ICSI treatment appear to be affected by higher frequency of chromosomal rearrangements than the general population. Categories with greater risk were represented by men with sperm cell count <20 x 10(6) sperm/ml, and women with history of pregnancy loss.

Adult↗

Course of ovarian hyperstimulation syndrome in 19 intact twin pregnancies after assisted reproduction techniques, with a case report of severe thromboembolism.

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted reproduction techniques using in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI). Its etiology has still not yet been fully resolved. Human chorionic gonadotrophin, administered exogenously as well as produced endogenously during pregnancy, is responsible for the onset of OHSS, and high levels of estradiol appear to worsen the condition. In this case series, the course of mild to severe OHSS was evaluated in 19 intact twin pregnancies after IVF/ICSI. Another serious complication associated with OHSS is thromboembolic events. In these cases, the pregnancy can be protected through anticoagulation treatment, but there may be exceptions to this. This series includes a case of bilateral thrombosis of the internal and external jugular veins in the 7th gestational week in a twin pregnancy after OHSS and ICSI, with termination of the pregnancy in the 9th gestational week due to progressive thrombosis during anticoagulation therapy.

Adult↗

The prognostic value of basal luteinizing hormone:follicle-stimulating hormone ratio in the treatment of patients with polycystic ovarian syndrome by assisted reproduction techniques.

One of the main endocrinological disturbances in patients with polycystic ovarian syndrome (PCOS) is the increased baseline concentrations of luteinizing hormone (LH) and consequently a high LH:follicle-stimulating hormone (FSH) ratio. The aim of this study was to assess the relationship between the baseline LH:FSH ratio with the stimulation response and the miscarriage risk in PCOS women stimulated for assisted reproduction techniques (ART) with and without gonadotrophin-releasing hormone analogue (GnRHa). Two groups of PCOS patients were analysed retrospectively. Group A (n = 20, 20 cycles) consisted of women stimulated with human menopausal gonadotrophin (HMG), and group B (n = 128, 162 cycles) comprised women stimulated with buserelin-long/HMG. LH and FSH concentrations were measured during the early follicular phase (days 4-6) in a preceding spontaneous or progestin-induced cycle. The following parameters were assessed: number of follicles developed, number of oocytes obtained and percentage of mature oocytes, as well as number of abortions and live births. In group A, the baseline LH:FSH ratio was correlated inversely with the number of follicles developed (P < 0.05), the number of oocytes obtained (P < 0.05) and the percentage of mature oocytes (P < 0.05). In group B, no correlation was found between the LH:FSH ratio and the number of follicles and oocytes, because their numbers were relatively constant irrespective of the baseline LH:FSH ratio, but a significant inverse correlation was noted with the percentage of mature oocytes (P < 0.001). However, a comparison of the slopes of the curve indicated a better correlation between the LH:FSH ratio and the percentage of mature oocytes in group A than in group B (P < 0.05). These findings were also confirmed when patients were subdivided according to the LH:FSH ratio (< 3 or > or = 3). Furthermore, in women who miscarried, the mean LH:FSH ratio was significantly higher than in women having a live birth. In conclusion, in PCOS patients stimulated with HMG, a high basal LH:FSH ratio appears to have an adverse effect on the number of follicles and oocytes, as well as on oocyte maturity. On the other hand, the administration of GnRHa in the long protocol seems to reverse this detrimental effect on follicle and oocyte development. Furthermore, a higher LH:FSH ratio seems to predict a greater possibility for miscarriage, despite the use of GnRHa.

Abortion, Spontaneous↗

Use of assisted reproductive techniques for treatment of ejaculatory disorders.

Ejaculatory disorders can interfere with the fertility of young adults who suffer from spinal cord injury, have type I diabetes mellitus or have undergone retroperitoneal or intrapelvic operations. Following an overview of causes and treatment of ejaculatory disorders, the data of our centre are presented. From a group of 37 patients with genuine loss of seminal emission, 15 men and their wives were offered a combined treatment of rectal probe electro-ejaculation and artificial reproductive techniques. No serious complications occurred. During 40 cycles with intracorporeal insemination and 11 cycles with extracorporeal fertilization techniques, seven pregnancies were achieved, representing a pregnancy rate of 46% per couple and 14% per cycle for all cycles. Five healthy children were born, all following extracorporeal insemination. The 'take-home baby rate' for this population and for this technique is 45%. In vitro fertilization (IVF) led to one birth, intracytoplasmic sperm injection (ICSI) achieved four live births out of three pregnancies, one being a twin gestation. Since our successes are due to the use of extracorporeal insemination techniques, these are now incorporated in a new, more rational treatment protocol.

Ejaculation↗

The effects of oxidative stress on outcomes of assisted reproductive techniques.

PURPOSE: To investigate the impact of oxidative stress on pregnancy success by monitoring malondialdehyde levels in follicular fluid. METHODS: Forty five couples were enrolled in this prospective study. Following long protocol of GnRH analogues and r-FSH treatment, oocyte retrieval and intracytoplasmic sperm injection were performed. Malondialdehyde levels were assayed by thiobarbutiric acid reacting substances test. Student's t-test and chi(2) test were used for statistical analysis. RESULTS: Patients were divided into two groups; group I (pregnancy positive, n = 20), group II (pregnancy negative, n = 25). There was no statistical significant difference in terms of age, infertility period, FSH levels on the third day, number of oocytes retrieved and fertilization rates between the two groups. Pregnancy rates were found to be decreasing in higher malondialdehyde levels. CONCLUSION: Malondialdehyde can be used as a marker of oxidative stress and a potential marker in predicting assisted reproductive techniques outcome.

Adult↗

Critical evaluation of human blastocysts for assisted reproduction techniques and embryonic stem cell biotechnology.

Critical examination of 30 blastocysts by transmission electron microscopy (TEM) reveals cellular features not usually evident, including abnormalities of cell structure and aberrations such as multinucleation, internal fragmentation, phagocytic or degenerating cells. Invariably, such blastocysts are inactive and delay or fail to expand and hatch in vitro. Hatching seems to be a major problem in ageing blastocysts due to inactivity of the surface epithelium of trophoblast cells that do not stretch and expand. These lack surface microvilli and contractile tonofilaments that anchor on to specialized cell junctions such as desmosomes. Trophoblast expansion and consequent thinning of the zona is a prerequisite to proper hatching aided by the hydrostatic pressure in the blastocoele and by specialized cells at hatching points. Proper assessment of the inner cell mass is required if a healthy population of cells is to be harvested for embryonic stem cell culture. An inactive blastocyst is obviously not good material and could have a defective inner cell mass (ICM). Normally approximately 3-5% of cells are mitotic in blastocysts and arrested cell division is also an indicator of inactivity. An attempt has been made to evaluate blastocyst internal structure for both assisted reproduction techniques and embryonic stem cell biotechnology.

Biotechnology↗

Assisted reproductive techniques in patients with Klinefelter syndrome: a critical review.

OBJECTIVE: To summarize the existing experience with the use and success rate of assisted reproductive techniques (ART), in particular testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI), in Klinefelter patients. DESIGN: A systematic review of the literature, including all published case reports to date. PATIENT(S): Thirty-nine reported successful pregnancies fathered by nonmosaic Klinefelter patients. MAIN OUTCOME MEASURE(S): The overall risk of transmitting a chromosomal abnormality to the offspring of Klinefelter patients. RESULT(S): In nonmosaic and mosaic Klinefelter patients, chromosomally normal sperm cells can be extracted from testicular tissue and used for ICSI. CONCLUSION(S): The application of ART to Klinefelter patients can be recommended as a method to achieve reproduction in this selected infertility patient cohort.

Chromosome Aberrations↗

Third-trimester ultrasound dating algorithms derived from pregnancies conceived with artificial reproductive techniques.

OBJECTIVE: To derive an accurate formula for ultrasound estimation of gestational age in late pregnancy. METHODS: A database of 123 singleton pregnancies conceived by artificial reproductive techniques with third-trimester ultrasound measurements was studied. Biometry variables included the fetal head circumference (HC) and femur length (FL). The dataset was equally divided into a derivation sample and a target sample. To derive the equations of best fit, regression analysis was used, with true menstrual age as the dependent variable and fetal biometry measurements as independent variables. The formulae were tested on the target set and the menstrual age estimates were compared with the actual menstrual age. Clinical performance was estimated in terms of systematic and random errors, absolute errors and their 95% CI values. RESULTS: The menstrual ages at time of scanning ranged from 26 to 41 weeks, with a mean of 33 weeks. The best performing derived formula was a combination of HC and FL. This had a random error of 7.5 days and prediction errors within a 95% confidence limit of -13 to +17 days. With FL only, the random error was 8.2 days, whereas using the HC only yielded a random error of 9.4 days. CONCLUSIONS: Ultrasound estimation of gestational age in late pregnancy is better than indicated by older publications. It is more accurately estimated by combining the HC with the FL than by using the FL measurements alone.

Algorithms↗

Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique--a prospective, randomized, double-blind study.

BACKGROUND: In primates, androgens can play a synergistic role with FSH in promoting the early follicular recruitment, which is critical in assisted reproduction technique programmes. OBJECTIVE: To assess whether poor responders can benefit from androgen application. METHODS: Inclusion criteria were a previous poor ovarian response to controlled ovarian stimulation and a decreased hormonal ovarian reserve. Selected women were randomized to receive either transdermal application of testosterone (n = 24) or placebo (n = 25) gel for 15 days before FSH treatment for a second IVF cycle. Similar GnRH analogue and equivalent FSH daily doses were used in both cycles. The primary outcome was the total number of oocytes retrieved. RESULTS: Testosterone gel application resulted in a significant increase in plasma testosterone levels but did not significantly improve the antral follicle count. Furthermore, after gel application, the main parameters of the ovarian response (numbers of pre-ovulatory follicles, total and mature oocytes and embryos) did not significantly differ between testosterone and placebo-treated patients. CONCLUSION: No significant beneficial effects of androgen administration on the ovarian response to FSH could be demonstrated. However, subsequent clinical trials are needed to determine whether an optimal dose and/or a longer duration of testosterone administration may be helpful.

Administration, Cutaneous↗

Induction of ovulation in women undergoing assisted reproductive techniques: recombinant human FSH (follitropin alpha) versus highly purified urinary FSH (urofollitropin HP).

This multicentre, open, randomized, study compared the efficacy and safety of recombinant follicle stimulating hormone (rFSH; follitropin alpha) with highly purified urinary human FSH (uFSH; urofollitropin HP) in women undergoing ovulation induction for assisted reproductive techniques. Following long down-regulation with buserelin, patients received two ampoules of 75 IU (150 IU) s.c. rFSH or highly purified uFSH for 6 days, after which the dose could be increased until they fulfilled the criteria for human chorionic gonadotrophin (HCG) administration. Of 168 patients recruited, 155 received at least one dose of FSH, and 137 received HCG [68: rFSH (85%); 69: uFSH (92%)]. Following oocyte retrieval and fertilization, up to three embryos were replaced/patient and luteal support was given. The mean number of oocytes retrieved/patient was 10.2 +/- 6.0 for rFSH patients compared with 10.8 +/- 6.1 in the uFSH group (not significant). There was a trend towards fewer ampoules used (22.3 +/- 6.5 versus 24.3 +/- 6.5), higher pregnancy (44.3 versus 41.4%) and live birth rates (33.8 versus 26.7%), as well as a lower miscarriage rate (0.0 versus 16.7%) in favour of rFSH. However, no significant differences in efficacy parameters were recorded. Ovarian hyperstimulation syndrome occurred in 8.6% and 7.9% of rFSH and uFSH patients respectively. In conclusion, this protocol was effective in inducing multiple follicular development and high numbers of oocytes were retrieved with both drugs.

Adolescent↗

Reproductive techniques in sheep.

This article reviews current methods of evaluating reproductive performance in the sheep industry. The reproductive technologies of breeding soundness examination, reproductive ultrasonography, estrus manipulation, artificial insemination, and embryo transfer are also extensively discussed. The veterinarian's current and future role in the application of these technologies is discussed.

Animals↗

Multiple birth prevalence in The Netherlands. Impact of maternal age and assisted reproductive techniques.

OBJECTIVE: To evaluate the impact of maternal age and use of fertility drugs on multiple birth prevalence from 1970 to 1995 in the Netherlands. STUDY DESIGN: A population-based survey was carried out in which data were collected from the Centraal Bureau voor Statistiek, the Institute of Medical Statistics and from all clinics for in vitro fertilization. RESULTS: In the last two decades, the prevalence of multiple births, especially of twin and triplet births, has increased significantly. Three possible explanations for this phenomenon are: (1) introduction of assisted reproductive techniques in combination with fertility drugs; (2) increasing maternal age; and (3) decreasing fecundity with increasing maternal age, resulting in more fertility treatments. A surplus of 1,366 twins was born in 1995 as compared to 1975. The expected excess of twins was 1,368, of which 104 (7.6%) were a result of the increase in total births in 1995, 583 (42.6%) were due to maternal age > 29 years, and, respectively, 330 (24.1%) and 351 (25.7%) twins were due to in vitro fertilization treatment and intrauterine insemination. CONCLUSION: The delay in achieving pregnancy and the use of fertility-promoting therapies profoundly affect the prevalence of multiple pregnancies in a given country. The general population should be informed of this risk.

Adult↗

The transmission of mitochondrial DNA following assisted reproductive techniques.

Mitochondria, among other functions, generate energy in the form of ATP. The chondrial genome, located within each mitochondrion, encodes some of the polypeptides associated with the electron transfer chain (ETC) and ATP production. Transcription and replication of mitochondrial DNA (mtDNA) is dependent upon the import of transcription and replication factors encoded by the nucleus. Certain point mutations and large-scale deletions to mtDNA can be either severely debilitating or lethal. The transmission and inheritance of mtDNA [not readable: see to offspring is strictly regulated and specific to each species. In many mammalian systems, paternal mtDNA is eliminated very early during embryonic development. However, it is possible that the paternal molecule could be extruded to those cells destined to become trophoblasts and may act as a regulator of embryonic cell fate. Furthermore, the increasing use of more sophisticated assisted reproductive techniques has led to the incorporation of extraneous mtDNA in both the reconstructed oocyte and embryo with transmission to the offspring at varying degrees.

Adenosine Triphosphate↗

Influence of ovarian stimulation on the detection of human papillomavirus DNA in cervical scrapes obtained from patients undergoing assisted reproductive techniques.

OBJECTIVE: To determine whether gonadotropin stimulation influences the detection of human papillomavirus (HPV) DNA in cervical scrapes. DESIGN: Prospective, controlled study. SETTING: Tertiary care infertility clinic. PATIENT(S): Two hundred ninety-four patients enrolled in an IVF or IUI program. Two thousand two hundred sixty-two women from an ongoing screening study who were of similar age served as a control group. INTERVENTION(S): Cervical scrapes were obtained with a cytobrush before and after ovarian stimulation with gonadotropins. MAIN OUTCOME MEASURE(S): Human papillomavirus status was assessed with a general primer (GP) polymerase chain reaction (PCR) using the GP5+/GP6+ system. In GP-PCR-positive samples, high-risk HPV types were identified with a cocktail of digoxigenin-labeled oligonucleotides. Viral load was evaluated by semiquantitative analysis of the PCR products. RESULT(S): The prevalence of high-risk HPVs was 7.8% before stimulation and 6.8% after stimulation and, thus, was similar to the prevalence in controls (8.4%). Twenty-nine patients were positive for high-risk HPVs: 14 were positive before and after stimulation, 6 were negative before and positive after stimulation, and 9 were positive before and negative after stimulation. Positivity for high-risk HPVs and viral load did not correlate directly with serum estrogen levels. CONCLUSION(S): Ovarian stimulation has no significant effect on the prevalence of HPV DNA in cervical scrapes obtained from patients undergoing assisted reproductive techniques.

Adult↗

GnRH agonist as luteal phase support in assisted reproduction technique cycles: results of a pilot study.

BACKGROUND: The aim of the study was to investigate whether intranasal (IN) administration of a GnRH agonist could provide luteal support in IVF/ICSI patients. METHODS: Controlled ovarian hyperstimulation (COH) was performed using hMG/FSH and a GnRH antagonist. Patients were then randomly allocated to either 10,000 IU hCG, followed by vaginal administration of micronized progesterone (3x 200 mg/day) (group A), or 200 microg IN buserelin followed by either 100 microg every 2 days (group B), or 100 microg every day (group C), or 100 microg twice a day (group D), or 100 microg three times a day (group E). Luteal support was continued for 15 days. RESULTS: Twenty-three patients were randomized. Groups B and C were discontinued prematurely in view of the short luteal phase. The luteal phase was significantly shorter in groups B, C and D, whereas group E was comparable with group A, 13.5 and 13.0 days, respectively. In the mid-luteal phase, median progesterone levels were significantly lower in groups B, C and D, whereas group E was comparable with group A, 68.9 and 98.0 ng/ml, respectively. Estradiol (E2) was significantly reduced in groups B and D but sustained in group E. In the hCG group, LH levels were undetectable (<0.1 IU/l), whereas LH was detectable and significantly higher in groups C, D and E. Two pregnancies were obtained in the hCG group (two of five), one ectopic and one ongoing. Three pregnancies were obtained in group E, one miscarriage and two ongoing twin pregnancies (three of five). CONCLUSION: IN administration of buserelin may be effective in triggering follicular maturation and providing luteal phase support in patients undergoing assisted reproduction techniques (ART).

Administration, Intranasal↗