Why Are the Proportions of In-Vitro Fertilisation Interventions for Same Sex Female Couples Increasing?

Same-sex female couples who wish to become pregnant can choose donor insemination or in-vitro fertilization (IVF)—a technique intended for infertile women. In general, women in same-sex female partnerships are no more likely to be infertile than those in opposite sex partnerships. This article investigates data available from the Government Regulator of UK fertility clinics—the Human Fertilization and Embryology Authority, which is the only data available worldwide on same-sex female couples and their fertility choices. IVF is increasing both in absolute numbers and relative proportions year on year in the UK, compared to licensed donor insemination for same-sex female couples. As IVF has greater human and financial costs than donor insemination, policies should not encourage it as the first choice for fertile women requiring sperm. Commercial transactions are taking place where fertile lesbians receive cut price, and arguably unnecessary, IVF intervention in exchange for selling their eggs to be used for other infertile customers. If women are not told about the efficacy of fresh vs. frozen semen, and the risks of egg ‘sharing’ or intra-couple donation, exploitation becomes possible.

Fertility and subfertility

This chapter covers issues related to fertility and subfertility. It starts with lifestyle assessments that should be done as part of preconceptual care, and explains the psychological effects and counselling for subfertility alongside both male and female factors that affect difficulties in conceiving. Tests and investigations are covered for both partners, and the role of the fertility nurse specialist is defined. Ovulation induction, assisted conception, inter-uterine insemination, and IVF are all described. Pre-implantation genetic diagnosis is given a brief overview, and the chapter also explores adoption and surrogacy. Fertility preservation and the role of the Human Fertilization and Embryology Authority are covered.

P–295 Does endometriosis affect oocyte quality? An analysis of 13 627 donor oocyte recipient and autologous IVF cycles

Study question Does endometriosis affect live birth following donor oocyte recipient versus autologous in vitro fertilisation (IVF) cycle. Summary answer There was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient versus autologous IVF cycle. What is known already For infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis when compared to tubal factor infertility. It has been debated that lower pregnancy rates following IVF in endometriosis is due to both oocyte quality and the endometrium. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study using donor oocyte recipient model where the recipient were women with endometriosis. We compared the LBR after oocyte recipient cycle with autologous IVF in women with endometriosis Study design, size, duration We obtained anonymised dataset of all the IVF cycles performed in the UK since 19991 from the Human Fertilization and Embryology Authority (HFEA). Data from 1996 to 2016 comprising a total of 13 627 donor oocyte recipient and autologous IVF cycles with endometriosis and no other cause of infertility were analysed. Participants/materials, setting, methods Data on all women with endometriosis undergoing fresh or frozen IVF treatment cycles were analysed to compare the LBR between donor oocyte recipient and autologous treatment cycles. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryo transferred, fresh and frozen cycle. Main results and the role of chance There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh cycles compared to women undergoing fresh autologous IVF cycles (31.6% vs. 31.0%; odds ratio, OR 1.03, 99% CI 0.79 – 1.35). After adjusting for confounders listed above, there was no significant difference in LBR in women undergoing donor oocyte recipient fresh cycles versus fresh autologous ART cycles (aOR 1.06, 99% CI 0.79 – 1.42). There was no significant difference in the LBR in women with endometriosis undergoing frozen donor oocyte recipient cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs. 24.0%; OR 0.77, 99% CI 0.47 - 1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing frozen donor oocyte recipient cycles compared with autologous frozen embryo transfer cycles (aOR 0.84, 99% CI 0.50 - 1.41). Limitations, reasons for caution Although the analysis was adjusted for several potential confounders, there was no information on classification of endometriosis to allow adjustment. Wider implications of the findings: The current study design does not indicate endometriosis has an impact on oocyte quality given that the outcomes in donor oocyte recipient cycles are comparable with autologous IVF cycles. These findings need to be further studied and validated. Trial registration number Not applicable

P-295 Does endometriosis affect oocyte quality? An analysis of 13 627 donor oocyte recipient and autologous IVF cycles

Study question Does endometriosis affect live birth following donor oocyte recipient versus autologous in vitro fertilisation (IVF) cycle. Summary answer There was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient versus autologous IVF cycle. What is known already For infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis when compared to tubal factor infertility. It has been debated that lower pregnancy rates following IVF in endometriosis is due to both oocyte quality and the endometrium. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study using donor oocyte recipient model where the recipient were women with endometriosis. We compared the LBR after oocyte recipient cycle with autologous IVF in women with endometriosis Study design, size, duration We obtained anonymised dataset of all the IVF cycles performed in the UK since 19991 from the Human Fertilization and Embryology Authority (HFEA). Data from 1996 to 2016 comprising a total of 13 627 donor oocyte recipient and autologous IVF cycles with endometriosis and no other cause of infertility were analysed. Participants/materials, setting, methods Data on all women with endometriosis undergoing fresh or frozen IVF treatment cycles were analysed to compare the LBR between donor oocyte recipient and autologous treatment cycles. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryo transferred, fresh and frozen cycle. Main results and the role of chance There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh cycles compared to women undergoing fresh autologous IVF cycles (31.6% vs. 31.0%; odds ratio, OR 1.03, 99% CI 0.79 – 1.35). After adjusting for confounders listed above, there was no significant difference in LBR in women undergoing donor oocyte recipient fresh cycles versus fresh autologous ART cycles (aOR 1.06, 99% CI 0.79 – 1.42). There was no significant difference in the LBR in women with endometriosis undergoing frozen donor oocyte recipient cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs. 24.0%; OR 0.77, 99% CI 0.47 - 1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing frozen donor oocyte recipient cycles compared with autologous frozen embryo transfer cycles (aOR 0.84, 99% CI 0.50 - 1.41). Limitations, reasons for caution Although the analysis was adjusted for several potential confounders, there was no information on classification of endometriosis to allow adjustment. Wider implications of the findings The current study design does not indicate endometriosis has an impact on oocyte quality given that the outcomes in donor oocyte recipient cycles are comparable with autologous IVF cycles. These findings need to be further studied and validated. Trial registration number Not applicable

Time-lapse imaging of human embryos fertilized with testicular sperm reveals an impact on the first embryonic cell cycle

Testicular sperm is increasingly used during in vitro fertilization treatment. Testicular sperm has the ability to fertilize the oocyte after intracytoplasmic sperm injection (ICSI), but they have not undergone maturation during epididymal transport. Testicular sperm differs from ejaculated sperm in terms of chromatin maturity, incidence of DNA damage, and RNA content. It is not fully understood what the biological impact is of using testicular sperm, on fertilization, preimplantation embryo development, and postimplantation development. Our goal was to investigate differences in human preimplantation embryo development after ICSI using testicular sperm (TESE-ICSI) and ejaculated sperm. We used time-lapse embryo culture to study these possible differences. Embryos (n = 639) originating from 208 couples undergoing TESE-ICSI treatment were studied and compared to embryos (n = 866) originating from 243 couples undergoing ICSI treatment with ejaculated sperm. Using statistical analysis with linear mixed models, we observed that pronuclei appeared 0.55 h earlier in TESE-ICSI embryos, after which the pronuclear stage lasted 0.55 h longer. Also, significantly more TESE-ICSI embryos showed direct unequal cleavage from the 1-cell stage to the 3-cell stage. TESE-ICSI embryos proceeded faster through the cleavage divisions to the 5- and the 6-cell stage, but this effect disappeared when we adjusted our model for maternal factors. In conclusion, sperm origin affects embryo development during the first embryonic cell cycle, but not developmental kinetics to the 8-cell stage. Our results provide insight into the biological differences between testicular and ejaculated sperm and their impact during human fertilization.

The role of seminal plasma extracellular vesicles in changes in the morphofunctional characteristics of human spermatozoa

For a long time, the role of seminal plasma during human fertilization remained underestimated. Numerous studies related to the development of different methods for human embryo in vitro cultivation were gener-ally concerned with the quality of male and female gametes. However, in recent years, the development of Omix technologies provided a new insight into great seminal plasma influence on the morphofunctional characteristics of spermatozoa. This is especially true for the regulatory function of extracellular vesicles secreted by male reproductive tract cells. In this work, we attempted to analyze current data on the influence of extracellular seminal plasma vesicles on the morphofunctional characteristics of spermatozoa to solve male infertility topical issues. The review includes studies by foreign and Russian research groups that werу conducted within the past 5 years and found in PubMed, Google Scholar, and Cochrane Library databases. Very few studies demonstrate that seminal plasma vesicles act as functional regulators of male fertility and their dysfunction may lead to infertility. The use of seminal plasma extracellular vesicles in clinical practice may significantly increase the success of IVF programs, especially in impaired spermatogenesis. Keywords: extracellular vesicles, exosomes, biomarkers, seminal plasma, spermatozoa, assisted reproductive technology, cell biology, morphology

An Examination into the Embryo Disposal Practices of Human Fertilization and Embryology Authority Licenced Fertility Centers in the United Kingdom

When fertility centers dispose of embryos, how should this be done? Current regulatory guidelines by the Human Fertilisation and Embryology Authority state that, when terminating the development of human embryos, a clinic should act with sensitivity, taking account of the embryo’s “special status” and respecting the interests of the gamete providers and recipients. As yet, it is unclear as to how and to what extent this achieved within fertility clinics in the UK. Resultantly, this paper examines the largely undocumented domain of embryo disposal practice. By undertaking an empirical study into policy and procedure and noting divergence in clinic practice, it then comments on the ethical implications of these protocols for patients and practitioners. Specifically, this paper argues for a more holistic approach to embryo disposal. An approach that effectively meets the requirements of the lab, is respectful of the “special status” of the human embryo, and, perhaps most importantly, reflects the multifaceted needs of the patient.

Peculiarities of Legal Regulation of the Use of Genomic Technologies in Embryology and Artificial Fertilization in the UK

The development of modern medicine is based on the development of high-tech treatment methods. One of such methods includes the application of genomic research that in Russia is not inferior, but in many ways superior to the achievements of Western scientists. However, legal regulation, or rather lack of such regulation in our state prevents comprehensive application of advanced techniques in practice. In order to solve this issue, it becomes relevant to study the experience of foreign countries in order to take into account their flaws and gaps in legal regulation to deal with the debate over problems that may be associated with the application of advanced techniques. The paper considers the use of genomic technologies in the UK in the field of embryology and artificial fertilization as one of the most open areas for genomic editing in modern medicine. The paper elucidates the issue of obtaining and withdrawal (revoking or suspending) of the license by organizations that provide medical services in the field of embryology and artificial human fertilization. The authors also deal with the issue of the formation of specialized bodies, e.g. appeals committees in the Human Fertilisation and Embryology Department, dealing with narrow issues. The authors have chosen legal regulation of the issue under consideration in Britain because it appears to be the most liberal regulation as compared with the regulation applied in the other States and even under international law. This, in turn, creates grounds for fears, disputes and discussions in the expert community, which is also of particular interest to the forthcoming Russian law-making and law enforcement. For the purposes of the study, the authors analyze the provisions of the Human Fertilisation and Embryology Act in terms of their applicability both in the UK and in Russia and examine expert opinions regarding the issues under consideration. Based on the work done, the authors propose to implement the model of legal regulation under which both children who appeared as a result of genomic editing and donors are to be informed of the application of this method.

A novel homozygous mutation of phospholipase C zeta leading to defective human oocyte activation and fertilization failure

STUDY QUESTION Is a novel homozygous phospholipase C zeta (PLCζ), c.1658 G>C; p. R553P mutation in the C2 domain associated with the outcomes of recurrent fertilization failure after ICSI? SUMMARY ANSWER PLCζ, c.1658 G>C led to defective human oocyte activation and fertilization failure, while this mutation in the C2 domain of PLCζ did not compromise concentration, motility and chromosome ploidy of sperm. WHAT IS KNOWN ALREADY Sperm-specific PLCζ is now widely considered to be the physiological stimulus that evokes intracellular calcium (Ca2+) oscillations, which are essential for egg activation during mammalian fertilization. Thus far, few genetic studies have shown that different point mutations in the PLCζ gene are associated with male infertility. STUDY DESIGN, SIZE, DURATION This was a basic medical research to assess pathogenicity for novel mutation in the C2 domain of PLCζ during human fertilization. PARTICIPANTS/MATERIALS, SETTING, METHODS Single-cell omics were applied to analyze the DNA methylation state of the fertilization failure oocytes and the ploidy of the patient’s sperm. Whole genome sequencing data for the patient were analyzed for mutations in PLCζ. Sanger sequencing confirmed the presence of a rare variant, and then the mutant and wild-type PLCζ mRNA were injected to observe oocyte activation. MAIN RESULTS AND THE ROLE OF CHANCE The fertilization failure oocytes (n = 4) were triploid and lacking proper DNA demethylation. The whole genome sequencing analysis revealed a novel missense homozygous mutation in PLCζ, c.1658 G>C; p. R553P, which leads to the conversion of arginine 553 to proline. This point mutation does not affect the production of the corresponding protein in sperm. However, microinjection of the mRNA transcribed from the PLCζ R553P mutation gene failed to trigger oocyte activation and the subsequent embryo development. LIMITATIONS, REASONS FOR CAUTION Only one patient with PLCζ mutations was available because of its rare incidence. WIDER IMPLICATIONS OF THE FINDINGS Notably, we discovered a novel homozygous mutation in PLCζ, which results in an abnormal conformation at the C2 domain of the PLCζ protein. Our findings indicate an essential role of PLCζ in human fertilization and the requirement of a normal structure of C2 domain in PLCζ-mediated physiological function. STUDY FUNDING/COMPETING INTEREST(S) This project is funded by the National Natural Science Foundation of China (31571544, 31871482, 31871447) and National Key Research and Development Program (2018YFC1004000, 2017YFA0103801). All authors declared no competing interests. TRIAL REGISTRATION NUMBER Not applicable.

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

Male infertility affects half of infertile couples and, currently, a relevant percentage of cases of male infertility is considered as idiopathic. Although the male contribution to human fertilization has traditionally been restricted to sperm DNA, current evidence suggest that a relevant number of sperm transcripts and proteins are involved in acrosome reactions, sperm‒oocyte fusion and, once released into the oocyte, embryo growth and development. The aim of this review is to provide updated and comprehensive insight into the molecular biology of spermatogenesis, including evidence on spermatogenetic failure and underlining the role of the sperm-carried molecular factors involved in oocyte fertilization and embryo growth. This represents the first step in the identification of new possible diagnostic and, possibly, therapeutic markers in the field of apparently idiopathic male infertility.