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PubMed2007

Having a child to save a sibling: reassessing risks and benefits of creating stem cell donors.

This manuscript assesses the risks, benefits, and ethical concerns regarding the use of assisted reproductive techniques (ART) to create a new donor for stem cell transplantation. We address ethical literature, the medical and psychosocial impact on patient, donor, family, and medical caregivers, and the appropriate decision-making process. We conclude that the use of ART to create a stem cell donor can be ethically acceptable. The decision to conceive a donor has medical and psychosocial implications. The family is the appropriate decision-maker and must consider risks and benefits to all parties with input from medical caregivers.

Abortion, Eugenic↗

PubMed2003

Medically assisted reproduction and second-trimester maternal serum marker screening for Down syndrome.

OBJECTIVES: To evaluate the effect of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) on total hCG, free ss-hCG, AFP and unconjugated estriol (uE3) used as markers for second-trimester Down syndrome maternal serum screening. METHODS: Second-trimester maternal sera from 1515 singleton pregnancies (970 by IVF, 545 by ICSI) were compared with control sera (21 014 cases). Free ss-hCG, total hCG, AFP and uE3 were compared between the control group and the medically assisted reproduction groups. The percentages of at-risk patients (>/=1/250) were also compared. RESULTS: No differences in values of the maternal serum markers were observed between the medically assisted and control groups. When maternal age was taken into account, the screen-positive rate for Down syndrome screening did not differ between the two groups. CONCLUSION: Patients undergoing assisted reproduction techniques can be counseled for maternal serum Down syndrome screening with the same efficacy as patients with naturally conceived pregnancies.

Adult↗

PubMed2003

Conjoined twins in a triplet pregnancy: early prenatal diagnosis with three-dimensional ultrasound and review of the literature.

We report two cases of conjoined twins complicating a triplet pregnancy diagnosed by two-dimensional ultrasound in the first trimester and evaluated further by three-dimensional ultrasound. A review of the literature over the last 30 years revealed 11 other cases diagnosed prenatally by ultrasound. Overall, three (23%) of these 13 pregnancies were achieved by assisted reproductive techniques and 10 (77%) were diagnosed before 18 weeks. Four women opted for termination of the whole pregnancy and three were managed expectantly, with two delivering before 32 weeks. Two monochorionic pregnancies underwent selective feticide with intrauterine demise of the non-conjoined fetus in both cases. All four dichorionic pregnancies undergoing selective termination or spontaneous embryo reduction to singleton in the first trimester resulted in term delivery of the non-conjoined fetus. The rare condition of conjoined twins in a triplet pregnancy poses a significant obstetric challenge from both diagnostic and management points of view. Accurate determination of chorionicity in these cases plays a critical role in determining management and outcome.

Adult↗

PubMed2000

SNAREs in mammalian sperm: possible implications for fertilization.

Soluble N-ethylmalameide-sensitive factor attachment protein receptor (SNARE) proteins are present in mammalian sperm and could be involved in critical membrane fusion events during fertilization, namely the acrosome reaction. Vesicle-associated membrane protein/synaptobrevin, a SNARE on the membrane of a vesicular carrier, and syntaxin 1, a SNARE on the target membrane, as well as the calcium sensor synaptotagmin I, are present in the acrosome of mammalian sperm (human, rhesus monkey, bull, hamster, mouse). Sperm SNAREs are sloughed off during the acrosome reaction, paralleling the release of sperm membrane vesicles and acrosomal contents, and SNARE antibodies inhibit both the acrosome reaction and fertilization, without inhibiting sperm-egg binding. In addition, sperm SNAREs may be responsible, together with other sperm components, for the asynchronous male DNA decondensation that occurs following intracytoplasmic sperm injection, an assisted reproduction technique that bypasses normal sperm-egg surface interactions. The results suggest the participation of sperm SNAREs during membrane fusion events at fertilization in mammals.

Acrosome Reaction↗

PubMed2007

Developmental, behavioral, and physiological phenotype of cloned mice.

Cloning from adult somatic cells has been successful in at least ten species. Although generating viable cloned mammals from adult cells is technically feasible, prenatal and perinatal mortality is high and live cloned offspring have had health problems. This chapter summarizes the health consequences of cloning in mice and discusses possible mechanisms through which these conditions may arise. These studies have further significance as other assisted reproductive techniques (ART) also involve some of the same procedures used in cloning, and there are some reports that offspring generated by ART display aberrant phenotypes as well. At the moment, the long-term consequences of mammalian cloning remain poorly characterized. Data available thus far suggest that we should use this technology with great caution until numerous questions are addressed and answered.

Animals↗

PubMed1993

Simultaneous swim-up/swim-down of sperm in assisted reproduction procedures.

PURPOSE: High-quality motile human spermatozoa were obtained following treatment of semen by simultaneous swim-up into medium and swim-down into an isotonic 40% Percoll solution. RESULTS: This procedure was significantly better than the swim-up method and comparable to discontinuous Percoll gradient centrifugation. Recovery rates of motile sperm were 35% for swim-up, 65% for Percoll gradient centrifugation, and 73% for swim-up/swim-down. CONCLUSION: The swim-down sperm was inferior to the swim-up sperm in its upward migration capacity but superior in morphology. Spermatozoa obtained by the swim-up/swim-down procedure demonstrated fertilizing ability in IVF, and clinical pregnancies were established. The simultaneous swim-up/swim-down procedure offers an alternative efficient method of simple separation of high-quality motile sperm for various assisted reproduction techniques.

Cell Separation↗

PubMed1996

Heterotopic pregnancy and assisted reproduction--an update.

PURPOSE: Heterotopic pregnancy, an extremely rare event in the past, has become a common complication of assisted reproduction techniques. METHODS AND RESULTS: This serious sequella of IVF/ET or GIFT is probably the result of ovarian hyperstimulation and the transfer of several embryos into the uterus or tubes of a preselected population suffering from mechanical infertility. The techniques and medium used for embryo transfer may also be involved. Delayed diagnosis resulting in rupture, hemorrhage, and emergency intervention with its serious consequences is being reported in nearly half of the cases. CONCLUSIONS: The prognosis for a viable intrauterine pregnancy, however, is good, and these combined pregnancies have produced a living child in about 70% of cases. A High index of suspicion, repeated ultrasounds, and early intervention are mandatory to salvage the viable intrauterine pregnancy and avoid maternal mortality.

Female↗

PubMed1996

Factors responsible for multiple pregnancies after ovarian stimulation and intrauterine insemination with gonadotropins.

PURPOSE: The present study was undertaken in order to analyze possible factors that could be responsible for multiple pregnancies in normoovulatory women undergoing superovulation with gonadotropins and intrauterine artificial insemination. METHODS: We retrospectively analyzed several clinical parameters in patients that achieved gestation with this treatment. Patients were divided into two groups depending on sperm origin (husband and donor sperm). Furthermore, they were subclassified as follows: (a) cycles resulting in single pregnancies (n = 366), (b) cycles ending in multiple pregnancies (n = 126), and (c) a control group composed of unsuccessful cycles (n = 366). RESULTS: In cycles employing husband's sperm, the age, number of cycles necessary to reach pregnancy, serum estradiol (E2) levels, and number of follicles were significantly (P < 0.05) different in multiple pregnancies compared to single or nonpregnant cycles. In donor insemination, women with multiple pregnancies were significantly younger than nonpregnant patients. There was a significant increase in the number of follicles developed (P < 0.00001) and serum E2 levels on the day of hCG (P < 0.05) in multiple compared to single pregnancies and unsuccessful cycles. The number of motile sperm in the insemination specimen was not different among the established groups. When both types of treatments were grouped, pregnant patients were significantly (P < 0.00001) younger than women with failed cycles. In addition, multifetal pregnancies were significantly (P < 0.05) more frequent in women < 30 years old. E2 production was significantly (P < 0.00008) higher in twin and multifetal pregnancies than in single or nonpregnant cycles. Follicular development was also significantly (P < 0.00001) higher in twin and multifetal pregnancies compared to failed cycles. CONCLUSIONS: The results suggest that young women (< 30 years) who develop more than six follicles with E2 > 1000 pg/ml when stimulated with gonadotropins are at higher risk of multiple gestation. These data may be helpful in preventing this undesired complication of assisted reproduction techniques.

Adult↗

PubMed1995

Antiovarian antibodies and their effect on the outcome of assisted reproduction.

PURPOSE: To compare the presence in levels of antiovarian antibodies (AOAb) in the pre- and postovulatory stage from serum of infertile patients undergoing intrauterine insemination (IUI) or in vitro fertilization (IVF) with outcome of the procedures. RESULTS: Serum from 36 women undergoing IUI, 36 women undergoing IVF and 25 fertile, healthy controls were assayed for the presence of AOAb by a commercially available ELISA kit. AOAb was positive in 59.7% of infertile women, while none of the fertile controls were positive for AOAb. The levels of these antibodies increased as the patient age and the number of treatment attempts increased. Though the presence of AOAb did not affect oocyte recovery rate, it resulted in decreased fertilization rate, cleavage rate, and pregnancy rate in infertile women. CONCLUSIONS: Our studies suggest that AOAb may be a cause of infertility and presence of these antibodies could have adverse effects on the outcome of assisted reproductive techniques.

Adult↗

PubMed2005

Role of the leukemia-inhibitory factor gene mutations in infertile women: the embryo-endometrial cytokine cross talk during implantation--a delicate homeostatic equilibrium.

Locally secreted cytokines of both the embryonic and the endometrial origin control the implantation process. The defects in their signaling that lead to unfavorable environment within the uterus may cause embryo implantation failure. The leukemia inhibitory factor (LIF), interleukin-11 (IL-11) as well as IL-12/IL-15/IL-18 system are regarded to be important signaling vectors. LIF plays an essential role in the preimplantation embryo development and the blastocyst implantation and its gene mutations in women contribute to the implantation failure and subsequent infertility. IL-11 signaling has been shown to be required for the uterine decidualization response as well as for the hatching and attachment of blastocysts. The IL-12/IL-15/IL-18 system interacts with endometrial leukocytes, particularly with NK cells, and influences directly the local angiogenesis and tissue remodeling. Differences in the levels of endometrial leukocytic subpopulations and in the patterns of intra-uterine cytokine concentrations that are observed between fertile and infertile women contribute to infertility probably by affecting the embryonic maternal dialogue during the implantation and early placentation period. Focusing on this cross talk promises to open new era in assisted reproduction techniques that will be based on diagnostics of missing signaling molecules and impairments of uterine receptivity as well as on therapeutic applications of individualized embryo culture and transfer media.

Cytokines↗

PubMed2000

Y chromosome microdeletion screening in infertile men.

Molecular analysis of Y-chromosomal microdeletions is routinely performed in the work-up of male infertility, in order to establish a diagnosis and for genetic counseling of the couple, since such microdeletions are transmitted to the male offspring. The review of published data shows that microdeletions are relatively common in patients with azoospermia or severe oligozoospermia, with wide variations in the reported deletion frequency depending mainly on the selection criteria. In general, patients with proximal deletions, involving the AZFa and/or the AZFb region show severe defects of spermatogenesis with a high prevalence of Sertoli cell only syndrome, while deletions of the distal AZFb and of the AZFc region can be compatible with residual spermatogenesis. Microdeletions have been only sporadically found in normozoospermic patients. For the time being the molecular analysis of microdeletions of the Y chromosome is indicated in infertile patients with sperm concentration <5 x 10(6)/ml and in men undergoing assisted reproduction techniques, since the genetic defect and, most probably, the related infertility problem will be transmitted to the sons.

Gene Deletion↗

PubMed2000

Effects of cancer and anti-neoplastic treatment on the human testicular function.

Men with testicular neoplasia (TN) and Hodgkin's disease (HD) are those who more frequently require treatment for fertility because these malignancies affect patients during the reproductive age and because the early diagnosis and the improved anti-neoplastic treatments cure most of these patients. Although some of them can father a child spontaneously, assisted reproductive techniques allow fatherhood to patients with severe spermatogenesis impairment and this possibility has raised concern about the long-term consequence of the testicular damage induced by chemo- and/or radiotherapy. This paper reviews the effects of cancer per se and of anti-neoplastic treatments on gonadal function, sperm aneuploidy rate and sperm DNA integrity. A debate is still open as to whether TN or HD per se may impair spermatogenesis. Many studies have shown that this is the case, albeit others have challenged this view. Chemo- and/or radiotherapy affects negatively gonadal function, rendering almost all patients azoospermics. However, spontaneous pregnancies and a high degree of spermatogenesis recovery occur with time. A large body of literature on sperm chromosome complement suggests an increased rate of structural and numerical chromosome abnormalities in patients with cancer during anti-neoplastic treatment. A minority of them has, however, shown that this effect disappears with time. An interesting and relatively new aspect is the study of sperm DNA integrity in patients with TN and HD particularly following chemo- and/or radiotherapy. The scanty information available seems to suggest that these patients have a permanent or at least a long-lasting DNA fragmentation in their spermatozoa.

Aneuploidy↗

PubMedDate not supplied

Spontaneous transmission from a father to his son of a Y chromosome microdeletion involving the deleted in azoospermia (DAZ) gene.

Microdeletions of the so-called azoospermia factor (AZF) locus of the Y chromosome long arm (Yq) have been recognized as an etiological factor of severe oligozoospermia or azoospermia. Because of this, patients affected are generally infertile unless assisted reproductive techniques are used. We report the case of an oligozoospermic patient (proband) who inherited an extensive Yq microdeletion from his father through a spontaneous pregnancy. Leukocyte DNA was extracted using a commercially available kit. A total of 22 pairs of sequence-tagged site (STSs) based primers, spanning the entire AZF region, were used for the screening. Both the proband and his father carried a Yq microdeletion of the most distal AZF subregion (AZFc) where the deleted in azoospermia (DAZ) gene is located. The proband's father was a sixty-nine-yr-old man who had 3 other children, 2 females and 1 male. This case adds further evidence that the deletion of the DAZ gene is associated with different phenotypic expressions, including normal fertility.

Adult↗

PubMed2000

[Symptom of micro-orchism for fertility and endocrine testicular function].

BACKGROUND AND OBJECTIVE: There are no reliable findings regarding the frequency and etiology of the spermatogenetic and endocrine functional restrictions in the small testicle (microorchidism). This information is needed to properly assess the risk when multiple testicular biopsies for assisted reproduction techniques lead to further volume reduction. PATIENTS/METHODS: 535 patients consulting our andrological clinic were included into the study. Orchidometric findings were corelated to spermatological data. Furthermore, FSH, Inhibin B, LH, testosterone and 17 estradiol were analysed. In 116 cases extended andrological studies clarified the etiology of the microorchidism. RESULTS: 26.5% of the patients had a testicular volume < or = 12 ml, 67.1% were in the normal area, 6.4% show a testicular volume > 25 ml. Patients with small testicles had azoospermia in 44.6%, OAT-syndrome in 20.2% and endocrine hypogonadism in 19.8%. The most frequent causes were Klinefelter-syndrome, maldescensus testis, varicocele, secondary atrophies and idiopathic clinical pictures. CONCLUSIONS: Microorchidism is understood as a one-sided testicular volume < or = 12 ml in adult men. We consider the risky taking of tissue out of the small testicle as avoidable, if predictive diagnostic factors for the discovering of spermatozoa via operation are analysed. An androgen-substitution in microorchidism may be carried out in selected individuals.

Adult↗

PubMed2000

Poor semen quality from patients with malignancies does not rule out sperm banking.

Cancer therapy can further impair the already poor semen quality in cancer patients. This study evaluated the prefreeze and postthaw semen quality before treatment of patients with malignancies to examine the rationale for sperm banking for these men. Records of nine patients with different malignant tumors, who had been referred for sperm cryopreservation between 1982 and 1997, were reviewed and the results were compared with those of 50 normal healthy donors. Patients did not differ from donors in age, ejaculate volume, or duration of sexual abstinence. The total motile sperm count (median and interquartile range) was significantly different between patients and donors for prefreeze specimens (P = 0.026) and postthaw specimens (P = 0.008). Also, the percent motility was significantly lower in the patients as compared with the donors in prefreeze (P = 0.035) and postthaw specimens (P = 0.005). The percentage change in motility after thawing was also larger for patient samples (-54% versus -47%, P = 0.39). Other sperm motion characteristics did not significantly differ between the two groups except for postthaw curvilinear velocity (P = 0.01). This study concludes that fresh and frozen thawed semen from patients with malignant tumors is poor in quality but is still adequate for assisted reproductive techniques. As cancer therapy may further impair semen quality, patients should be offered the chance to bank sperm before undergoing cancer therapy.

Adolescent↗

PubMed2005

Recurrent cornual pregnancy after heterotopic cornual pregnancy successfully treated with systemic methotrexate.

This report concerns a recurrent spontaneous cornual pregnancy 2 years after selective feticide of a heterotopic cornual pregnancy which occurred after IVF for tubal pathology. The recurrent cornual pregnancy was treated successfully with systemic methotrexate. Assisted reproductive techniques, especially in patients with tubal pathology, and non-invasive management of cornual pregnancies may lead to a higher incidence of recurrence.

Abortifacient Agents, Nonsteroidal↗

PubMed2002

Heterotopic pregnancy at 16 weeks of gestation after in-vitro fertilization and embryo transfer.

We present an heterotopic pregnancy at 16 weeks of gestation following IVF/ET treatment with the ectopic pregnancy located in the left fallopian tube. Intra-abdominal bleeding secondary to an heterotopic pregnancy, causing acute abdominal pain and hemorrhagic shock, should be included in the differential diagnosis even in the second trimester of pregnancy, especially in patients, achieving conception with the use of assisted reproduction techniques.

Adult↗

PubMed2006

An immunohistochemical study in a fatality due to ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a complication occurring in the luteal phase of a menstrual cycle in which ovulation induction or ovarian hyperstimulation for assisted reproduction techniques has been performed. Our report concerns the death of a 31-year-old woman with primary infertility on recombinant follicle stimulating hormone therapy (Gonal-F) who developed a fatal adult respiratory distress syndrome. Immunohistochemical investigation of lung and uterine samples was performed utilizing monoclonal antibodies for antisurfactant apoprotein (PE-10) and polyclonal antibodies anti-IL-6, IL-8, IL-10, TNFalpha for lungs, and polyclonal antibodies anti-beta-HCG (human chorionic gonadotropin) for uterus. The knowledge of macroscopic and histologic findings should be of special interest for all those who perform autopsies in these victims. The exact pathogenesis of OHSS remains a mystery; so for the diagnosis of suspected OHSS, the forensic pathologist must use all the modern laboratory armament to validate the diagnosis in the extremely rare fatal cases due to this syndrome.

Adult↗