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PubMed2006

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↗

PubMedDate not supplied

[Commentary on the decision of the Constitutional Court of June 17, 1999 resolving the Recourse of Inconstitutionality no. 376/89 against the 35/1988 law of November on assisted reproduction techniques].

The author discusses the ruling by the Spanish Constitutional Court (116/99, 17 June) in the matter of the challenge on grounds of alleged inconstitutionality lodged against the Law on Assisted Reproduction Techniques back in 1989. Other circumstances concerning the application and development of said law are examined also and a detailed critical study is made of the legal points used in the Ruling. The article concludes with some thoughts on the main issues arising therefrom.

Abortion, Legal↗

PubMed2000

Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques.

The predictive value of sperm chromatin integrity for pregnancy outcome following in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) was studied in 24 men attending a university-based assisted reproductive techniques laboratory using the flow cytometric sperm chromatin structure assay (SCSA). The SCSA is a measure of the susceptibility of sperm DNA to low pH-induced denaturation in situ. The mean percentage of spermatozoa in the neat sample demonstrating DNA denaturation was significantly lower in the seven men that initiated a pregnancy (15.4 +/- 4.6, P = 0.01) than in the 14 men who did not initiate a pregnancy (31.1 +/- 3.2). No pregnancies resulted if > or =27% of the spermatozoa in the neat semen sample showed DNA denaturation. These data demonstrate that SCSA parameters are independent of conventional semen parameters. Furthermore, the SCSA may allow physicians to identify male patients for whom IVF and ICSI will be unlikely to result in pregnancy initiation.

Adult↗

PubMed2004

Exogenous luteinizing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques.

OBJECTIVE: To investigate the role of exogenous LH in controlled ovarian hyperstimulation for assisted reproductive technologies. DESIGN: Prospective randomized study. SETTING: SISMER fertility unit. PATIENT(S): Women showing a hyporesponsiveness to FSH under GnRH agonist down-regulation were randomized into three groups: group A (n = 54) received an increased dosage of FSH; group B (n = 54) was administered recombinant LH in addition to the increased dose of FSH; group C (n = 22) was given additional FSH and LH using hMG as a combined drug. Fifty-four age-matched women with no need to increase the FSH dose were included as a control group (D). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation and live birth rate per started cycles. RESULT(S): In group B, the pregnancy and implantation rates were statistically higher when compared with groups A and C and did not differ from the control group for normal response. The live birth rate was similar in groups B and D but was half as high in groups A and C. CONCLUSION(S): Hyporesponsiveness to FSH could be related to iatrogenic LH deficiency that, in turn, could affect oocyte competence. Addition of a small amount of recombinant LH is able to rescue oocyte competence to produce viable embryos.

Adult↗

PubMed1997

Comparison of second trimester biometry in singleton and twin pregnancies conceived with assisted reproductive techniques.

The objective of this study was to investigate the size of singleton vs twin pregnancies at the time of a second trimester dating scan. The analysis included 86 infants from 63 pregnancies achieved with assisted reproductive techniques, comprising 40 singletons and 46 twins. Measurements of second trimester biparietal diameter (n = 85) and femur length (n = 74) were plotted against the precisely known gestational age. A common regression line was calculated for each parameter and the residuals for singletons and twins were compared. Gestational age and weight at birth were also analysed for each group. There was no significant difference between singletons and twins in biparietal diameter or femur length in second trimester. In contrast, twins had a lower mean birthweight, gestational age at birth, and weight-for-gestational age centile compared with singletons. Singleton babies from these pregnancies had an average birthweight centile of 49.8% (i.e. close to the median for spontaneously conceived pregnancies in our population). We concluded that the same pregnancy dating charts can be used for singletons and twins. At corresponding gestational age, twins are smaller than singletons at birth because of slower growth in the third trimester.

Anthropometry↗

PubMedDate not supplied

Intrauterine insemination with husband's semen as alternative to other assisted reproduction techniques.

The objectives of this study was to assess the efficacy and clarify how many intrauterine insemination cycles can justifiably be proposed, in terms of cost and benefits for the patient, as alternative to other assisted reproduction procedures. Two hundred and twenty infertile couples were referred to our centre and six intra-uterine insemination cycles in combination with controlled ovarian hyperstimulation were proposed for them. A total of 650 treatment cycles were completed. The indications of intra-uterine insemination were male factor (147 couples), cervical factor (31 couples), male and cervical factor (30 couples) and unexplained infertility (12 couples). Superovulation was induced in 92 patients with human menopausal gonadotrophins, in 90 with clomiphene citrate, in 22 with FSH HP, while in 16 patients the intra-uterine inseminations were carried out during spontaneous cycles. Considering the entire population, a mean monthly pregnancy rate equal to 8.9% was obtained and a cumulative pregnancy rate equal to 39% at the end of six intra-uterine insemination cycles. In particular, in the patients treated with HMG+hCG, a mean monthly pregnancy rate equal to 10.9% and a cumulative pregnancy rate to 46% at the end of the six cycles were obtained. In conclusion, when the indications allow, we believe it is justified to propose six cycles of intra-uterine insemination in combination with controlled ovarian hyperstimulation with HMG and hCG. The theoretical probability of success at the end of six cycles has proved comparable and advantageous in terms of cost and risks for the patient, if compared with other assisted reproduction techniques.

Adult↗

PubMed2000

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↗

PubMed1995

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↗

PubMed1998

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↗

PubMed2004

Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic.

BACKGROUND: Little is known about the prevalence of specific depressive and anxiety disorders in women before a new course of assisted reproductive technology treatment. Few studies have adopted the proper psychiatric diagnostic procedures. METHODS: All consecutive women visiting the assisted reproduction clinic of a university-affiliated medical centre, with the intention of starting a new assisted reproduction treatment course, were recruited. A psychiatrist made a diagnosis of psychiatric disorders using a structured interview, the Mini-International Neuropsychiatric Interview (MINI). RESULTS: Of a total of 112 participants, 40.2% had a psychiatric disorder. The most common diagnosis was generalized anxiety disorder (23.2%), followed by major depressive disorder (17.0%), and dysthymic disorder (9.8%). Participants with a psychiatric morbidity did not differ from those without in terms of age, education, income, or years of infertility. Women with a history of previous assisted reproduction treatment did not differ from those without in depression or anxiety. CONCLUSIONS: Depressive and anxiety disorders were highly prevalent among women who visited an assisted reproduction clinic for a new course of the treatment. Demographic features and a history of previous assisted reproduction treatment were not risk factors for these psychiatric morbidities in the assisted reproduction clinic.

Academic Medical Centers↗

PubMed2002

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↗

PubMed1999

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↗

PubMed2006

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↗

PubMed2005

[Infertility treatment and endometriosis -- risk and benefit of assisted reproductive techniques].

Infertility is a common clinical finding in patients with endometriosis. Surgical procedures have shown some benefit, whereas endocrine treatment alone does not improve fertility. Although assisted reproduction is superior to observation only, the pregnancy rate after IVF is lower than in patients with tubal or idiopatic infertility. The grade of endometriosis correlates to the pregnancy rate. The role of endometriomas in assisted reproduction is still a matter of debate. Ultralong stimulation protocols have no advantage to standard long luteal phase regimens. In particular in multifactor infertility IVF seems to be the treatment option of choice.

Endometriosis↗

PubMed2005

Congenital abnormalities in children born after assisted reproductive techniques: how much is associated with the presence of infertility and how much with its treatment?

Although there is increasing evidence to link couples with infertility undergoing all assisted reproductive technologies, particularly intracytoplasmic sperm injection (ICSI), and congenital abnormalities, the reasons remain unclear. Much evidence suggests that infertility itself might be a risk factor, and further long-term follow-up studies involving different possible control groups will help determine whether these abnormalities are directly related to treatment.

Child↗

PubMed2000

[The influence of infertility treatment and assisted reproduction techniques on multiple pregnancy rates].

It has to be remembered that pregnancies resulting from assisted reproductive technologies are more complicated that spontaneous pregnancies. There are higher rates of spontaneous abortions, ectopic, and multiple pregnancies. This work summarizes the latest year's experiences from the best world's clinics with multifetal pregnancy incidence in assisted reproductive technologies programs.

Female↗

PubMed2000

Recent trends in assisted reproductive techniques and associated outcomes.

OBJECTIVE: We examined recent trends in success rates for assisted reproduction and determined the influence of changes in patient selection and treatment characteristics on these trends. METHODS: We collected baseline information and abstracted treatment-related details and outcomes on 1244 couples accepted for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) at three clinics in greater Boston from 1994-1998. RESULTS: Delivery rates per initiated cycle improved significantly from 14.9% for IVF and 20.6% for GIFT in 1994-1995 to 22.5% for IVF and 28.0% for GIFT in 1997-1998 (P < or = .001). After adjusting for female age, the two treatment-related variables that appeared most likely to explain this trend were decreased use of GnRH agonists in short course (flare) regimens and increased use of highly purified forms of urinary gonadotropins. CONCLUSION: There were significant improvements in the success rates for IVF and GIFT from 1994-1998 that correlated with changes in ovulation induction regimens.

Adult↗

PubMed1995

[Results, evolution of assisted reproduction techniques].

During the last decade IVF and other assisted conception treatment (ACT) methods have become an internationally accepted form of treatment of infertile couple. The final definition of success following ACT is the couple who having received treatment have a live child. As IVF treatment gradually becomes more successful and as the number of babies born as a result of this treatment increases more attention is being focused on the outcome of ACT pregnancies. Recent and futur development of ACT are related.

Female↗