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Successful paternity with microassisted fertilization after total body irradiation-based conditioning for autologous bone marrow transplantation.

We present the case of a 20-year-old man with acute lymphoblastic leukemia who received chemotherapy with vincristine, adriamycin, cyclophosphamide, methotrexate, teniposide (VM-26), and bleomicin, followed by an autologous bone marrow transplantation after total body irradiation (TBI)-cyclophosphamide-based conditioning regimen. At 14 years, despite the severe oligoasthenospermia, he fathered a healthy child by assisted reproductive technique (ART) consisting in controlled ovarian hyperstimulation of the patient's wife, transvaginal ovum pick up and microinjection of the ovum with a previously isolated sperm cell from the patient (intracytoplasmatic sperm injection, ICSI). As far as we know, that is the first documented case of successful paternity using microassisted fertilization with ICSI technique in a patient submitted to TBI-based bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical strategies to avoid multiple pregnancies in assisted reproduction.

Multiple pregnancies following assisted reproductive techniques (ART) became an epidemic in the early nineties. Since then, most European countries have tried to apply restrictive policies to avoid multiples and high order multiples as far as possible. Those pregnancies may cause severe consequences to both the fetuses and mother. Economic, social and ethical dilemmas are also avoidable if caution is exercised when using ART to achieve those pregnancies. When restrictive policies are used in ovulation induction and in vitro fertilization, the results show a clear reduction in the number of MP maintaining satisfactory rates.

Female↗

Reproductive outcomes in women with uterine anomalies.

PURPOSE: Because of diagnostic improvements in the evaluation of uterine anomalies, more patients desirous of pregnancy come to clinicians with identified uterine anomalies. It is desirable for the family physician, internist, and obstetrician/gynecologist to provide accurate information during preconceptional counseling of these patients. This review attempts to provide a concise summary of the current English-speaking literature concerning the reproductive outcome in women with uterine anomalies following both natural conceptions and those pregnancies occurring with assisted reproductive techniques (ART). METHODS: A literature review of reproductive anomalies and pregnancy outcomes was performed using PubMed databases. Obstetrical outcomes were compiled from the medical literature and compared with the known rates of pregnancy outcomes in subjects presumed to have normal uterine anatomy. RESULTS: In general, obstetrical complications, such as preterm delivery and first trimester miscarriage, are higher in women with abnormal uteri. Women with an arcuate uterus have a similar reproductive outcome to women with a normal uterus. The unicornuate uterus has the poorest overall reproductive outcome, and the septate uterus has an increased miscarriage rate. The didelphic uterus, historically thought to have no adverse reproductive outcomes, also has poor obstetrical outcomes. Didelphic, bicornuate, unicornuate, and septate uteri have lower pregnancy rates in ART. CONCLUSIONS: Women with uterine anomalies have poorer reproductive outcomes and lower pregnancy rates with all conceptions whether spontaneous or induced with ART compared with women with normal uteri.

Female↗

Features associated with reproductive ageing in female rhesus monkeys.

BACKGROUND: The specific aims were to determine the effects of maternal age on the meiotic and developmental competence of oocytes and incidence of chromosomal anomalies in oocytes from a population of fertile rhesus monkeys. METHODS: Monkeys were divided into two age groups (4-15 and 16-26 years of age) and underwent ovarian stimulation for collection of oocytes. RESULTS: In the older, compared with younger, monkeys, serum basal concentrations of FSH were elevated (P < 0.05), peak concentrations of estradiol during a stimulation cycle were diminished (P < 0.05), and mean numbers of oocytes retrieved following ovarian stimulation were markedly (P < 0.05) reduced. There were no significant maternal age-related impairments in oocyte maturation, fertilization or blastocyst development. Both abnormal numbers of whole chromosomes, as well as free chromatids, were detected in a limited number of rhesus oocytes. CONCLUSIONS: Similarities between female rhesus monkeys and women in several features associated with reproductive ageing, in conjunction with our ability to perform IVF and other assisted reproductive techniques in monkeys, demonstrate the suitability of these animals for studies on human reproductive ageing and maternal age-related infertility. Although maternal age-related impairments in oocytes were not evident prior to implantation, further studies may reveal more subtle impairments, manifested during post-implantation development.

Aging↗

Changes in twinning rate: Italy 1950-1996.

BACKGROUND: In the wide-ranging debate about the potential monitors of population fertility, twinning rate has been considered a candidate. In the developed countries, a decline in spontaneous twinning rate began around 1950 and continued until the late 1970s. The decrease in mean maternal age at delivery and the number of children per family have been considered as possible reasons for the decrease. The rise in twinning rates, which began in the 1980s, is probably due to the spread of assisted reproduction, at least for older mothers. METHODS: The temporal trend in twinning rate and the relationship with maternal age at delivery and birth order in the Italian population were analysed. RESULTS: The recent increase in twinning rate can be mainly attributed to the recourse to assisted reproduction techniques, as demonstrated by the twinning frequency among older primiparae. The twinning rate recently observed in young mothers approximates to the value of the 1950s, which is assumed to represent a 'natural' fertility condition. CONCLUSIONS: On the assumption that twinning is an indicator of fertility, and hence of population fitness, the present data seem to suggest that natural fertility has been slightly increasing in the Italian population.

Birth Order↗

Assisted reproductive technology in Europe, 2000. Results generated from European registers by ESHRE.

European results of assisted reproductive techniques from treatments initiated during 2000 are presented in this fourth annual report. Data were collected mainly from pre-existing national registers. From 22 countries, 569 clinics reported 279 267 cycles: IVF 126 961, ICSI 99 976, frozen embryo replacement (FER) 45 800 and oocyte donations (OD) 6530. In nine countries where all clinics reported to the register, a total of 142 174 cycles were performed in a population of 166 million, corresponding to 856 cycles per million inhabitants. After IVF and ICSI, the distribution of transfer of one, two, three and >or=4 embryos was 12.1, 46.7, 33.3 and 6.8%, respectively. Huge differences existed between countries. For IVF, the clinical pregnancy rate per aspiration and per transfer was 24.7 and 28.4%, respectively. For ICSI, the corresponding rates were 26,6% and 28,7%. These figures represent increases of 0.7 and 0.8% compared with 1999. The distribution of singleton, twin, triplet and quadruplet deliveries for IVF and ICSI combined was 73.6, 24.4, 2.0 and 0.04%. This gives a total multiple delivery rate of 26.4%. The range of triplet deliveries after IVF and ICSI ranged from 0.3 to 7.0% between countries. Compared with 1999, the number of reported cycles was increased by 8% and the clinical pregnancy rate per transfer was increased by 0.7% after IVF and by 0.8% after ICSI. The total multiple delivery rates after IVF and ICSI remain unchanged during the last 4 years.

Adolescent↗

Is the CAG repeat of mitochondrial DNA polymerase gamma (POLG) associated with male infertility? A multi-centre French study.

BACKGROUND: Recent data emphasized the implication of polymerase gamma (POLG) CAG repeats in infertility, making it a very attractive gene for study. A comparison of POLG CAG repeats in infertile and fertile men showed a clear association between the absence of the usual 10-CAG allele and male infertility, excluding azoospermia. It has also been suggested that the POLG gene polymorphism should be considered as a possible contributing factor in unexplained couple infertility where semen parameters are normal. In this study, we investigated the POLG CAG repeats, in a well-defined population of patients with severe male factor infertility. METHODS: We conducted a large study of POLG CAG repeats in 433 infertile and 91 fertile, normozoospermic and healthy males. In all subjects, phenotypic data, including semen parameters, hormonal status and clinical profiles, were available. RESULTS: Thirteen 'homozygous mutants' (3%) were found among the 433 idiopathic infertile patients. The follow-up of the 13 'homozygous mutant' resulted in pregnancy for more than half of the couples, through assisted reproductive techniques or even spontaneously. In addition, one 'homozygous mutant' was identified in 91 fertile men (1.1%) CONCLUSION: Under our conditions, our study does not confirm any relationship between the polymorphic CAG repeat in the POLG gene and male infertility.

Adult↗

Assisted reproductive technology in Europe, 2001. Results generated from European registers by ESHRE.

European results of assisted reproductive techniques from treatments initiated during 2001 are presented in this fifth report. Data were collected mainly from already existing national registers. From 23 countries, 579 clinics reported 289 690 cycles with: IVF 120 946, ICSI 114 378, frozen embryo transfer (FER) 47 195 and egg donation (ED) 7171. Overall this represents a 4% increase since the year 2000. For the first time, results on European data on intra-uterine inseminations (IUIs) were reported from 15 countries. A total of 67 124 cycles [IUI husband'sperm (IUI-H) 52 949 and IUI donor sperm (IUI-D) 14 185] were included. In 12 countries where all clinics reported to the register, a total of 108 910 cycles were performed in a population of 131.4 million, corresponding to 829 cycles per million inhabitants. For IVF, the clinical pregnancy rate per aspiration and per transfer was 25.1 and 29.0%, respectively. For ICSI, the corresponding rates were 26.2 and 28.3%. These figures are similar to the results from 2000. After IUI-H, the clinical pregnancy rate was 12.8% in women <40 and 9.7% in women > or =40 years of age. After IVF and ICSI, the distribution of transfer of one, two, three and > or =4 embryos was 12.0, 51.7, 30.8 and 5.5%, respectively. Compared with the year 2000, fewer embryos were transferred, but huge differences existed between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 74.5, 24.0 and 1.5%, respectively. This gives a total multiple delivery rate of 25.5%, compared with 26.9% in the year 2000. The range of triplet deliveries after IVF and ICSI differed from 0.0 to 8.2% between countries. After IUI-H in women <40 years of age, 10.2% were twin and 1.1% were triplet gestations.

Age Distribution↗

The impact of successful assisted reproduction treatment on female and male mental health during transition to parenthood: a prospective controlled study.

BACKGROUND: The dynamics of mental health during the transition to parenthood have not been a focus of research. Our prospective longitudinal study was designed to reveal whether there are differences in mental health during the transition to parenthood between parents undergoing treatment with assisted reproduction techniques (ART) and those who conceive spontaneously. METHODS STUDY GROUP: 367 couples with a singleton ART pregnancy using their own gametes. CONTROL GROUP: 379 couples with a spontaneous singleton pregnancy. Men and women separately filled in questionnaires including the General Health Questionnaire: at the 18th-20th week of pregnancy, 2 months postpartum and 1 year postpartum (T3). The effect of social and child-related factors on mental health was examined. RESULTS: ART women had fewer depressive symptoms during pregnancy than controls, but at T3 their depressive symptoms were at the same level as seen in controls. Anxiety symptoms increased among control but not among ART women across the transition. ART men reported generally fewer mental health symptoms than their controls. Social and child-related stressors had negative impacts on mental health changes among control couples, whereas no impact was found among ART couples. CONCLUSIONS: Successful ART did not predict mental health problems during the transition to parenthood. Moreover, ART couples' mental health was remarkably resistant to social and child-related stress during the transition to parenthood.

Adult↗

Comparative birth weights of singletons born after assisted reproduction and natural conception in previously infertile women.

BACKGROUND: The possible interference of assisted reproduction techniques (ART) with epigenetic reprogramming during early embryo development has recently sparked renewed interest about the reported lower birth weight among infants born as a consequence of infertility treatments. However, the latter finding so far has relied on the comparison of the birth weight of infants conceived with ART to general population data. A more appropriate comparison group should involve pregnancies in infertile women after natural conception. Therefore, we compared neonatal birth weight data of infants born after various ART treatments, including intrauterine insemination (IUI), with those of previously infertile women achieving pregnancy after sexual intercourse. METHODS: Between August 1996 and March 2004 the data of all infertile women presenting in the infertility unit of the University Women's Hospital of Basel, Switzerland, were collected prospectively, adding up to 995 intact pregnancies and deliveries. The birth weight of all infants resulting from 741 singleton pregnancies were analysed with regard to the patients' characteristics, the occurrence of complications during pregnancy and the type of infertility treatment with which the pregnancies were achieved. RESULTS: Comparison of duration of pregnancy and birth weight of infants born after infertility treatment confirms a shorter pregnancy span and a lower mean birth weight in infants born after IVF and ICSI. If women with pregnancies after ART deliver before term, neonatal birth weight is significantly lower. CONCLUSIONS: There is a specific effect of ART, mainly IVF and ICSI, on both shortening the duration of pregnancy and lowering neonatal birth weight. Both these parameters seem to be interrelated consequences of some modification in the gestational process induced by the infertility treatment. Freezing and thawing of oocytes in the pronucleate stage had a lesser impact on pregnancy span and on neonatal birth weight.

Adult↗

Assisted reproductive technology in Europe, 2002. Results generated from European registers by ESHRE.

European results of assisted reproductive techniques (ART) from treatments initiated during 2002 are presented in this sixth report. Data was mainly collected from already existing national registers. From 25 countries, 631 clinics reported 324,238 treatment cycles with: IVF 122,634, ICSI 135,048, frozen embryo replacement (FER) 57 162, egg donation (ED) 7677, preimplantation genetic diagnosis/screening (PGD/PGS) 1563 and in vitro maturation (IVM) 154. Overall this represents a 12% increase since year 2001. For the second time, results on European data on intrauterine inseminations were reported from 17 countries. A total of 93,284 cycles [IUI-husband/partner (H), 78 505 and IUI-donor (D), 14,779] were included. In 13 countries where all clinics reported to the register, a total of 177,429 cycles were performed in a population of 193.7 million, corresponding to 916 cycles per million inhabitants. For IVF the clinical pregnancy rate per aspiration and per transfer was 26.0 and 29.5%, respectively. For ICSI the corresponding rates were 27.2 and 29.4%. These figures are marginally better than in 2001. After IUI-H the clinical pregnancy rate was 11.6% in women below 40 and 7.8% in women>or=40 years of age. After IVF and ICSI the distribution of transfer of 1, 2, 3 and 4 or more embryos was 13.7, 54.8, 26.9 and 4.7%, respectively. Compared with year 2001, less embryos were transferred, but huge differences existed between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 75.5, 23.2 and 1.3%, respectively. This gives a total multiple delivery rate of 24.5%, compared with 25.5% in year 2001. The range of triplet deliveries after IVF and ICSI varied from 0.0 to 5.2% between countries. After IUI-H in women below 40 years of age, 10.2% were twin and 1.3% triplet gestations.

Adult↗

Should ART be offered to HIV-serodiscordant and HIV-seroconcordant couples: an ethical discussion?

Increasingly, fertility clinics are offering their services to human immunodeficiency virus (HIV)-serodiscordant couples where the woman is seropositive. In the case of HIV-seroconcordant couples, there remains a general reluctance to provide treatment. This attitude to seroconcordant couples is reminiscent of that once widely held towards serodiscordant couples when the risk of vertical transmission rates in pregnant women was greater than 1-2%. Due to recent advances in HIV clinical care and assisted reproduction technique (ART) procedures directed at reducing the risk of viral transmission during gamete transfer, where good healthcare is available, the current risk rate has fallen to 1-2%. This article deals with the ethical arguments of those who remain opposed to offering HIV-serodiscordant and HIV-seroconcordant couples access to ART. Until these arguments have been addressed, clinics providing ART to such couples cannot be assured that their practices are ethical.

Attitude↗

Determination of twin zygosity using a commercially available STR analysis of 15 unlinked loci and the gender-determining marker amelogenin--a preliminary report.

BACKGROUND: The aim of this preliminary study was to estimate the accuracy of the zygosity determination in twin pregnancies. METHODS: Seventy-three sets of twin pregnancies were enrolled in this study, including 48 sets of twins resulting from assisted reproductive techniques (ART) and 25 sets of spontaneously conceived twins. Determination of zygosity was made by PCR-amplified short tandem repeat (STR) analysis with a commercially available panel, comprising 15 autosomal, codominant, unlinked loci and the gender-determining marker, amelogenin. Monozygotic (MZ) twins were determined when all these unlinked loci and the gender-determining marker were identical. Chorionicity and placenta were examined after delivery of the newborns to check their relationships to the twin zygosities. RESULTS: Three of 48 (6.25%) sets of twins produced by ART and 18 of 25 (72%) sets of spontaneously conceived twins were MZ. Monozygosity could be evaluated based on 'like sex' in spontaneously conceived twins, because they had a greater incidence of MZs than those produced by artificial reproductive techniques. The MZ prediction rate was 78.6%, and the overestimated rate was 21.4% if the monochorionic like-sexed twins (LST) had a grossly single placenta. The underestimated rate of MZs was 26.7% when the dichorionic LST had apparently separate placentas. CONCLUSION: With the DNA-based 15 STR analysis amplified in a multiplex PCR, the determination of the zygosity in multifetal pregnancies is not only cost and time saving but also yields greater sensitivity and precision than conventional methods.

Adult↗

Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART.

BACKGROUND: The relationship between early embryo post-implantation development in couples undergoing assisted reproductive techniques (ARTs) and sperm chromatin alterations has not been satisfactorily explained. The aim of this study was to assess the relationship between sperm DNA fragmentation in IVF/ICSI patients, sperm parameters (concentration, motility and morphology) and ART outcome, especially with regard to clinical pregnancy and pregnancy loss (spontaneous miscarriage or biochemical pregnancy). METHODS: DNA fragmentation was evaluated by TUNEL assay, performed on sperm suspensions after density gradient separation, in 132 men undergoing an ART cycle (82 IVF and 50 ICSI) and correlated with sperm parameters and ART outcome. RESULTS: A highly significant negative correlation was found between DNA fragmentation and sperm parameters. There was a close relationship between DNA fragmentation and post-implantation development in ICSI patients: the clinical pregnancy and pregnancy loss rates significantly differed between patients with high and low sperm DNA fragmentation (P = 0.007 and P = 0.009, respectively). CONCLUSIONS: Sperm DNA fragmentation seems to affect embryo post-implantation development in ICSI procedures: high sperm DNA fragmentation can compromise 'embryo viability', resulting in pregnancy loss.

Abortion, Spontaneous↗

ART outcome in HIV-infected patients.

BACKGROUND: To assess assisted reproductive technique (ART) outcome in couples affected by human immunodeficiency virus (HIV). METHODS: Intrauterine insemination (IUI), IVF and ICSI were performed in 85 couples affected by HIV between January 2000 and June 2005. RESULTS: In 33 of the 85 couples, women were HIV positive-the clinical pregnancy rate (CPR) and cancellation rate (CR) after 34 IUI cycles were, respectively, 25 and 18%. The CPR after 26 IVF and 30 ICSI cycles were, respectively, 37.5 and 18.8% with CRs of 38.5 and 46.7%, respectively. In 38 couples, men were infected-the CPR and CR after 85 IUI cycles were, respectively, 14.7 and 20%; 62 ICSI cycles were performed leading to CPR of 23.4% with a CR of 25%. In 14 couples, the two partners were infected: none of the four IUI cycles carried out was successful (CR, 20%); the CPR and CR after 35 ICSI cycles were, respectively, 12.5% with 31%. All children born had a negative HIV test. CONCLUSION: In couples affected by HIV, an acceptable pregnancy rate was obtained. The worst results were obtained when both partners were infected. The CR was elevated among HIV-infected couples.

Adult↗

Safety of sperm washing and ART outcome in 741 HIV-1-serodiscordant couples.

BACKGROUND: To evaluate the safety of sperm washing and assisted reproduction technique (ART) outcome offered to serodiscordant couples with a human immunodeficiency virus-1 (HIV-1)-positive male. METHODS: Sperm washing was performed and checked by RT-PCR on each semen sample before its fresh usage. Intrauterine insemination (IUI) or IFV/ICSI was offered according to fertility profile of each couple. Non-infected women underwent HIV testing 2 weeks before each procedure and for up to 6 months after. RESULTS: Seven hundred and forty-one couples entered the study of a possible 2011 serodiscordant couples counselled over 4 years. Superovulation and IUI were performed in 581 couples, where the pregnancy rate per cycle and pregnancy rate per couple were 19 and 78%, respectively, with multiple pregnancy rate being 4%. One hundred and sixty couples were treated by IVF/ICSI, where pregnancy rate per cycle and per couple were 22 and 41%, respectively, with multiple pregnancy rate being 10%. All female partners were still HIV-1 negative at follow-up. CONCLUSION: Sperm washing within a programme of reproductive counselling was proved to be safe in this large series of serodiscordant couples. The overall pregnancy rate (70.3%), independent of the procedure used (IUI or IVF/ICSI), justifies the effort of the medical team in setting up and implementing dedicated centres and of the individual patient in seeking a safe pregnancy.

Acquired Immunodeficiency Syndrome↗

Serum müllerian-inhibiting substance in Down's syndrome pregnancies.

BACKGROUND: To examine whether maternal serum levels of müllerian-inhibiting substance (MIS) differ in Down's syndrome and unaffected pregnancies. METHODS: Case-control study was conducted using stored serum from an antenatal screening programme. Sera from 25 Down's syndrome pregnancies were retrieved from -20 degrees C storage together with 125 unaffected controls individually matched for maternal age, weeks of gestation and duration of storage. Results were expressed in multiples of the gestation-specific median value (MoM) in controls. RESULTS: The median value in Down's syndrome pregnancies was 0.83 MoM (P = 0.77, two-tail Wilcoxon rank sum test). Among unaffected pregnancies, there was a statistically significant correlation between MIS and pregnancy-associated plasma protein-A (P < 0.05). MIS levels were elevated in pregnancies where assisted reproduction techniques had been used. CONCLUSION: There is no evidence for a substantial reduction in maternal serum MIS levels in Down's syndrome pregnancies. This study provides useful information regarding serum MIS levels in pregnancy.

Adult↗

Reproduction and fertility in human immunodeficiency virus type-1 infection.

Human immunodeficiency virus type-1 (HIV-1) affects mostly men and women in their reproductive years. For those who have access to highly active antiretroviral therapy (HAART), the course of HIV-1 infection has shifted from a lethal to a chronic disease. As a result of this, many patients with HIV-1 consider having offspring, as do other patients of reproductive age with chronic illnesses. This article summarizes the current knowledge on the presence of HIV in the male and female genital tract, the effects of HIV-1 infection and HAART on male and female fertility and the results of various assisted reproduction techniques (ART) in HIV-1-infected men and women who wish to have offspring.

Anti-HIV Agents↗