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Infertility treatment in women with epilepsy: A systematic review.

BACKGROUND: The impact of assisted reproductive technologies (ART) on seizure control in women with epilepsy remains incompletely understood. METHODS: A systematic review was conducted according to PRISMA guidelines. EMBASE, MEDLINE, CINAHL, Scopus, and the Cochrane Library were searched from inception to March 2025. Eligible studies included observational studies and case-based reports involving women undergoing infertility treatment. RESULTS: A total of 1216 publications were identified, of which four studies met the inclusion criteria, including case reports, a case series, and a cohort study. These studies included 16 women aged 25-46 years undergoing infertility treatment, all but one of whom had epilepsy. Interventions involved in vitro fertilization (IVF), ovulation induction, and hormonal therapies. Patients were treated with a range of antiseizure medications (ASMs), including carbamazepine, clobazam, lamotrigine, levetiracetam, oxcarbazepine, valproate, and zonisamide, either as monotherapy or in combination. Seizure frequency was generally stable, with most patients maintaining baseline seizure control. Seizure exacerbations were uncommon and primarily associated with hormonal therapy and reduced ASM levels, particularly reduced lamotrigine levels. Reported events included breakthrough seizures in the setting of decreased lamotrigine concentrations, seizure clusters associated with follitropin beta, and a new-onset seizure following dehydroepiandrosterone exposure. Across studies, multiple ART attempts resulted in live births with different ASM regimens, as well as in patients not receiving ASMs. CONCLUSION: Available evidence suggests that ART is feasible in women with epilepsy, with most patients maintaining stable seizure control. Hormonal therapy may affect ASM pharmacokinetics and seizure threshold, thereby warranting close monitoring. Larger prospective studies are needed to better define ASM-specific effects and optimize care.

Humans↗

Definition and causes of infertility.

Infertility is a common problem affecting one couple in six. It can be defined as the incapacity to fulfill pregnancy after reasonable time of sexual intercourse with no contraceptive measures taken. The evidence for changes in the prevalence of infertility is difficult to establish. This increase could be due to at least four factors: delayed childbearing, alterations in semen quality due to habits such as cigarette smoking and alcohol, changes in sexual behaviour and eliminations of most taboos. The study of infertile couple has always been focussed on different factors: ovulatory factor (present in about 20% of couples), utero-tubal peritoneal factor (present in ~30% of couples), semen migration factor (10% of cases) and male factor (30% of couples). Around 40% of all infertile couples exhibit a combination of factors and about 15% of couples may not display any objective alteration leading to a definite diagnosis. During the past two decades there have been three important changes in infertility practice. First, the introduction of assisted reproduction technologies has provided an opportunity to study basic reproductive processes. Second, societal changes have occurred such as the increase in the proportion of women over 35 years old seeking pregnancy. This fact is due to a later age for marriage and postponement of pregnancy. Third, the development of molecular biology and genetics has become very important for the study, diagnosis and assessment of couples, many of them considered until now as "unexplained infertile couples".

Journal Article↗

Nuclear-cytoplasmic interactions affect in utero developmental capacity, phenotype, and cellular metabolism of bovine nuclear transfer fetuses.

We generated a clone of bovine somatic cell nuclear transfer embryos using oocyte pools from defined maternal sources to study nuclear-cytoplasmic interactions. Nucleocytoplasmic hybrids were reconstructed with Bos taurus (Brown Swiss) granulosa cells and oocytes that contained B. taurus A (Simmental), B. taurus B (Simmental), or Bos indicus (Dwarf Zebu) cytoplasm. Another set of embryos was reconstructed with randomly selected Brown Swiss (B. taurus R) oocytes. Embryo transfer resulted in nine (12.5%), nine (13.8%), three (50%), and 11 (16.7%) Day 80 fetuses, of which eight (11.1%), three (4.6%), three (50%), and 10 (15.2%) were viable, respectively. The proportion of viable fetuses was affected by cytoplasm (likelihood ratio test, P < 0.02) and was higher for embryos with B. indicus cytoplasm than for the B. taurus A (P < 0.05) and B (P < 0.01) groups. Furthermore, the proportion of surviving Day 80 fetuses was reduced for B. taurus B as compared with B. taurus A and B. taurus R cytoplasm (P < 0.05 and P < 0.02). Body weight of nucleocytoplasmic hybrid fetuses was not significantly different from Brown Swiss control fetuses produced by artificial insemination (AI), but fetuses reconstructed with random cytoplasts of the same breed as the nuclear donor exhibited overgrowth (P < 0.01) and a higher coefficient of variation in weight. Furthermore, body weight, crown rump length, thorax circumference (P < 0.05), and femur length (P < 0.01) of fetuses with B. taurus A cytoplasm differed from fetuses with B. taurus R cytoplasms. Fetal skin, heart, and liver cells with B. indicus cytoplasm showed a greater increase in number per time period (P < 0.001) and oxygen consumption rate per cell (skin and liver, P < 0.001; heart, P < 0.08) in comparison with their counterparts with B. taurus A cytoplasm. These data point to complex oocyte cytoplasm-dependent epigenetic modifications and/or nuclear DNA-mitochondrial DNA interactions with relevance to nuclear transfer and other reproductive technologies such as ooplasmic transfer in human assisted reproduction.

Animals↗

Posthumous reproduction and the meanings of autonomy.

In recent years there has been considerable debate over the legal and ethical issues associated with posthumous reproduction. This article analyses recent cases and legal regulation of reproductive technologies in Australia. The issues associated with posthumous reproduction are explored through a consideration of the nature of an individual's interest in their reproductive material. The suitability of a property-based model as a means of conceptualising interests in reproductive material is explored. The article concludes that the issues in this area need to be analysed in terms of autonomy interests that are understood relationally.

Australia↗

New birth technologies: a social work approach to researching the psychosocial factors.

Developments in reproductive technology, notably in vitro fertilization and artificial insemination using donor sperm, are occurring at a rapid rate. Research into the psychosocial aspects of these developments has been minimal, as has been the contribution of social workers to this research. This paper reports the author's research and discusses a number of issues that have emerged as a result of a social work attempt to investigate the psychosocial factors.

Attitude of Health Personnel↗

Ultrastructural dynamics of human reproduction, from ovulation to fertilization and early embryo development.

This study describes the updated, fine structure of human gametes, the human fertilization process, and human embryos, mainly derived from assisted reproductive technology (ART). As clearly shown, the ultrastructure of human reproduction is a peculiar multistep process, which differs in part from that of other mammalian models, having some unique features. Particular attention has been devoted to the (1) sperm ultrastructure, likely "Tygerberg (Kruger) strict morphology criteria"; (2) mature oocyte, in which the MII spindle is barrel shaped, anastral, and lacking centrioles; (3) three-dimensional microarchitecture of the zona pellucida with its unique supramolecular filamentous organization; (4) sperm-egg interactions with the peculiarity of the sperm centrosome that activates the egg and organizes the sperm aster and mitotic spindles of the embryo; and (5) presence of viable cumulus cells whose metabolic activity is closely related to egg and embryo behavior in in vitro as well as in vivo conditions, in a sort of extraovarian "microfollicular unit." Even if the ultrastructural morphodynamic features of human fertilization are well understood, our knowledge about in vivo fertilization is still very limited and the complex sequence of in vivo biological steps involved in human reproduction is only partially reproduced in current ART procedures.

Embryonic Development↗

Cumulus oophorus extracellular matrix in the human oocyte: a role for adhesive proteins.

A viscous elastic matrix secreted by the cumulus oophorus cells represent the "extracellular matrix" surrounding the human mature oocyte obtained from assisted reproductive technology (ART). The cumulus matrix is involved in several reproductive processes, including the pick-up of the oocyte-cumulus complex by the oviduct, the final maturation of the ovum and sperm-egg interaction. As showed by some Authors, the cumulus matrix is rich in hyaluronan, as well as in other proteins including inter-alpha-trypsin inhibitor, a dermatan sulfate proteoglycan, and a pentraxin-3. Proteins and hyaluronan are linked together to form a meshwork comprised of granules and filaments. We found in human cumulus oocyte complexes the presence of specialized cells still capable of producing fibronectin and tenascin-c in the post-ovulatory period. Moreover, fibronectin and tenascin-c are present within the hyaluronan matrix at fertilization during the tubal sojourn of the ovum and the embryo. Since pentraxin3 is important in matrix stabilization and gamete interactions, a possible role for fibronectin and tenascin-c may be postulated in the final maturation of the ovum, in the tubal pick-up and in the complex dialogue with the tubal epithelium.

C-Reactive Protein↗

[Planned control of reproduction processes in industrialized cattle production].

Reference is made to the authors' own experience and to evaluated literature in an account of possibilities which so far have been explored for planned control of reproduction processes in industrialised cattle production. Synchronisation of oestrus in heifer has been found to be suitable for reproduction control even under conditions of industrialised production. The method has been in use on several farms. Synchronisation of oestrus in cow is an approach which still is in the process of translation into practice. Obtainable advantages, like those in the context of heifer, will include better job conditions. Systematic puerperal monitoring, too, will yield positive effects in controlling post-partum readiness of cow for reproduction. Results so far achieved include progress towards the introduction of a complex reproduction technology in cattle production. Before such complete system of reproduction control can be used, further studies are required into some fundamental aspects of the problem, including calving control, pregnancy examination, and gravidity hagiene.

Animals↗

Procreative liberty, embryos, and collaborative reproduction: a legal perspective.

This article discusses the implications of a constitutionally protected right to procreate using a wide range of reproductive choices made possible by noncoital reproductive technologies, including embryo freezing and donation and surrogate gestation. After establishing the constitutional basis for a positive right to procreate, it discusses the extent to which concerns about the welfare of embryos, offspring, donors, and surrogates justifies limitation on reproductive choice involving these technologies. While tangible harm to offspring and protection of the free choice of reproductive collaborators may justify regulation, moral condemnation of noncoital techniques and concerns about the reifying effects of their use are an insufficient basis for state restriction.

Child↗

Human-nonhuman chimeras: a regulatory proposal on the blurring of species lines.

The chimera of modern biotechnology is defined broadly as a single organism composed of a mixture of materials from two or more organisms possessing distinct genetic backgrounds. Unlike the United States, which does not regulate chimeras directly, Canada has responded to the unregulated pursuit of chimera technology by banning certain chimeras as part of comprehensive legislation designed to regulate human reproductive technologies. In 2004, the Canadian Parliament passed the Assisted Human Reproduction Act despite criticism urging greater legislative justification for the Act's provisions and modification to it statutory definitions. Because current regulatory mechanisms in the United States, including patent law and administrative oversight, fail to regulate chimera technology, the United States should enact new legislation, using Canada's legislation as a model, to prohibit embryonic chimeras and to regulate other human-nonhuman combinations. Unregulated biotechnology threatens to disrupt legal and social institutions; therefore, the United States must make a balanced effort now to protect the public interest.

Advisory Committees↗

Journal of Experimental & Clinical Assisted Reproduction: shaping the future of research and practice in reproductive endocrinology/infertility.

Journal of Experimental & Clinical Assisted Reproduction is an open access, online, peer-review journal publishing papers on all aspects of research into reproductive endocrinology, infertility, bioethics and the advanced reproductive technologies. The journal reports on important developments impacting the field of human reproductive medicine and surgery. The field exists as a sub-specialty of obstetrics & gynecology, focusing on the diagnosis and treatment of complex human reproductive problems. The continued growth of this relatively new field depends on quality research by proven scientists as well as junior investigators who, together, make contributions to this area of medical and surgical practice. The publishing revolution made possible by internet technology presages a bright future for continued interdisciplinary collaboration among researchers. Against this background, Journal of Experimental & Clinical Assisted Reproduction exists for the scientific community to facilitate this scholarly dialogue.

Journal Article↗

Semen technologies in dog breeding: an update.

Pure dog breeding is experiencing growing interest. Assisted reproductive technologies are each time demanded more by the small animal practitioner. In this paper different semen technologies are briefly reviewed under the perspective of the authors. In addition, new trends in the evaluation of canine ejaculates, developed in the laboratory of the authors are discussed. The existence of sperm subpopulations defined based both on kinematics and morphometric characteristics of the spermatozoa is now widely accepted by the scientific community. In the laboratory of the authors new, simpler and more straightforward statistical tools have been used to disclose the sperm subpopulation structure in the canine ejaculate. The study of the sperm subpopulation structure and its changes after cryopreservation has allowed us to gain an insight into the differences in freezeability among dogs, and also predict to a great extent the outcome of a cryopreservation procedure of a given semen sample. New techniques to evaluate early membrane changes have also been recently developed in our laboratory.

Animals↗

Previous miscarriages influence IVF and intracytoplasmatic sperm injection pregnancy outcome.

Previous conceptions are one predictor for the outcome of assisted reproductive technology procedures. Approximately 18-34% of clinical pregnancies following assisted reproduction procedures result in spontaneous abortion. The risk of such pregnancy loss is believed to increase with women's age, previous miscarriages and use of frozen-thawed embryos. This study analyses German IVF Registry data to examine the impact of previous miscarriages on the outcome of assisted reproduction procedures. The data set consists of a total of 174,909 assisted reproduction procedures performed between January 1998 and December 2000. Multiple logistic regression is used to assess the correlation between women's age, spousal/partner change, and infertility diagnosis. It is demonstrated that any previous miscarriage will increase the treatment-dependent miscarriage rate in assisted reproduction procedures. A significantly higher impact is shown for one previous miscarriage achieved by assisted reproduction procedures compared with spontaneous conception. Partner change is shown to have no specific impact on the treatment dependent miscarriage rate, whereas a statistically significant increase in miscarriages in all assisted reproduction procedures was found among women older than 34 years of age. Overall, the highest rate of treatment-dependent miscarriages was seen in assisted reproduction procedures with cryopreserved embryo transfer.

Abortion, Spontaneous↗

The new Italian IVF legislation.

Last February, the Italian Parliament gave final approval to a new Law regulating assisted reproduction technology. The new legislation fell short of the expectations of infertile couples and of all specialists in the field. There are three problems with the new Italian law; they involve social issues, human rights and the application of technology. The present paper focuses on the fact that the new rules infringe upon basic human rights and the proper application of IVF technology, because they mandate procedures that are against the best interest of the woman seeking pregnancy. The main point of controversy is the combination of a mandatory limit of three embryos for transfer, and an obligation to reimplant all produced embryos; cryopreservation of excess embryos is prohibited. Obviously, this decreases the chances of most women to achieve pregnancy, while at the same time it increases the number and complexity of procedures they need to undergo and may expose some to an unacceptable increase in the risk of multiple pregnancy. The new law is inspired by the desire to protect every newly produced embryo; this is a commendable aim, although it is in total opposition to a law passed over 25 years ago that liberalized voluntary termination of first trimester pregnancies. This means that today Italy has a law that protects every early, pre-implantation embryo, and another that allows the 'suppression' of every post-implantation one. From a technical point of view, given the low level of human fecundity, the only way to prevent the 'loss' of even one preimplantation embryo is to simply ban IVF altogether, an option that Italian legislators obviously did not have the courage to opt for. The tragedy is that Italian infertile couples are now confronted with new rules that not only severely limit the ability of physicians to correctly apply IVF technology, but are so confused that, depending on the interpretation, anyone may try to nullify the main ideological premise upon which the entire law has been structured.

Embryo Implantation↗

Progress in the management of tuboovarian abscesses.

The last 20 years have witnessed remarkable improvements in the treatment of tuboovarian abscesses. Gone are the days of significant mortality associated with ruptured and unruptured TOAs. Broad-spectrum antibiotics have enabled patients to be treated solely with medical therapy, avoiding the need for surgery. Operative intervention is still necessary in 25% of cases of unruptured TOAs, but the combination of conservative surgical procedures, such as unilateral salpingo-oophorectomy, and broad-spectrum antimicrobial agent therapy have reduced the need for total abdominal hysterectomy with bilateral salpingo-oophorectomy greatly. Although fertility after TOAs is compromised significantly, new advances in reproductive technology, including in vitro fertilization and donor egg transplantation, represent reproductive options for these women. Percutaneous drainage and laparoscopic treatment of TOAs are becoming popular treatment options, but prospective studies urgently are needed to assess their efficacy.

Abscess↗

Detection of HIV and HCV RNA in semen from Brazilian coinfected men using multiplex PCR before and after semen washing.

INTRODUCTION: Prolonged survival of patients under HAART has resulted in new demands for assisted reproductive technologies. HIV serodiscordant couples wish to make use of assisted reproduction techniques in order to avoid viral transmission to the partner or to the newborn. It is therefore essential to test the effectiveness of techniques aimed at reducing HIV and HCV loads in infected semen using molecular biology tests. METHODS: After seminal analysis, semen samples from 20 coinfected patients were submitted to cell fractioning and isolation of motile spermatozoa by density gradient centrifugation and swim-up. HIV and HCV RNA detection tests were performed with RNA obtained from sperm, seminal plasma and total semen. RESULTS: In pre-washing semen, HIV RNA was detected in 100% of total semen samples, whereas HCV RNA was concomitantly amplified in only one specimen. Neither HIV nor HCV were detected either in the swim-up or in the post-washing semen fractions. CONCLUSIONS: Reduction of HIV and/or HCV shedding in semen by density gradient centrifugation followed by swim-up is an efficient method. These findings lead us to believe that, although semen is rarely found to contain HCV, semen processing is highly beneficial for HIV/HCV coinfected individuals.

Adult↗

Reproduction in water buffalo: comparative aspects and implications for management.

The domestic buffalo occupies an important niche in many ecologically disadvantaged agricultural systems, providing milk, meat and draught power. Although buffalo can adapt to harsh environments and live on low quality forage, their reproductive efficiency is often compromised by such conditions. Climatic stress depresses ovarian cyclicity, oestrous expression and conception rates. Poor nutrition, usually related to seasonal fluctuations in availability and quality of feed, delays puberty and increases the duration of postpartum anoestrus. Management factors such as the system of grazing (free, tethered or none) and sucking by calves (restricted or ad libitum) also modulate reproductive functions. Finally, the skills and capabilities of farmers as well as the quality of support services such as artificial insemination and disease control also influence fertility. The relative importance of these factors vary greatly depending on ecological conditions and production systems. Improvement of reproductive efficiency therefore requires the identification of specific limiting factors under a given situation and the development and field testing of strategies for improvements and interventions that are sustainable with available local resources. The application of modern reproductive technologies in buffaloes requires an appreciation of their biology and reproductive physiology as well as the potentials and limitations under each specific production system.

Animal Husbandry↗

Ovarian stimulation of squirrel monkeys (Saimiri boliviensis boliviensis) using pregnant mare serum gonadotropin.

The application of assisted reproductive technologies (ART) to nonhuman primates has created opportunities for improving reproductive management in breeding colonies, and for creation of new animal models by genetic modification. One impediment to the application of ART in Saimiri spp. has been the lack of an effective gonadotropin preparation for ovarian stimulation. Pregnant mare serum gonadotropin (PMSG) is inexpensive and readily available, but its repeated use in rhesus monkeys has been associated with induction of a refractory state. We have compared PMSG to recombinant human follicle stimulating hormone (rhFSH) for controlled ovarian stimulation in Bolivian squirrel monkeys. Groups of mature squirrel monkeys received rhFSH (75 IU daily) or PMSG (250 IU twice daily) by subcutaneous injection for 4 d during the breeding season (November to January) or nonbreeding season (March to September). Serum estradiol (E2) was measured daily. Follicular growth was monitored by abdominal ultrasound. During the breeding season, PMSG induced a higher E2 response than did rhFSH, with mean E2 levels being significantly higher within 3 d of stimulation. Superior follicular development in PMSG animals was confirmed by abdominal ultrasonography. During the nonbreeding season, PMSG elicited a similar increase in serum E2 levels despite the fact that basal serum E2 is typically low during the nonbreeding season. Repeated use of PMSG (< or = 3 cycles of administration) produced no attenuation of the E2 response. We conclude that PMSG is highly effective for repeated cycles of controlled ovulation stimulation in the squirrel monkey.

Animals↗