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Fulltext Genetic analysis of the M2/ANXA5 haplotype as recurrent pregnancy loss predisposition in the Malay population

Ang KC, Kathirgamanathan S, Ch'ng ES, Lee YY, Roslani AL, Naidu B, et al.

J Assist Reprod Genet, 2017 Apr;34(4):517-524.
PMID: 28108842 DOI: 10.1007/s10815-017-0871-0

PURPOSE: The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out.
METHODS: A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and "late" fetal losses, and >15th gestation week subgroups.
RESULTS: Both male and female subjects had similar M2/ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers.
CONCLUSION: This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.
Reactive oxygen species-induced alterations in H19-Igf2 methylation patterns, seminal plasma metabolites, and semen quality

Darbandi M, Darbandi S, Agarwal A, Baskaran S, Dutta S, Sengupta P, et al.

J Assist Reprod Genet, 2019 Feb;36(2):241-253.
PMID: 30382470 DOI: 10.1007/s10815-018-1350-y

PURPOSE: This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction.
METHODS: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS
Fulltext Advancements in reprogramming strategies for the generation of induced pluripotent stem cells

Lai MI, Wendy-Yeo WY, Ramasamy R, Nordin N, Rosli R, Veerakumarasivam A, et al.

J Assist Reprod Genet, 2011 Apr;28(4):291-301.
PMID: 21384252 DOI: 10.1007/s10815-011-9552-6

Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells has emerged as an invaluable method for generating patient-specific stem cells of any lineage without the use of embryonic materials. Following the first reported generation of iPS cells from murine fibroblasts using retroviral transduction of a defined set of transcription factors, various new strategies have been developed to improve and refine the reprogramming technology. Recent developments provide optimism that the generation of safe iPS cells without any genomic modification could be derived in the near future for the use in clinical settings. This review summarizes current and evolving strategies in the generation of iPS cells, including types of somatic cells for reprogramming, variations of reprogramming genes, reprogramming methods, and how the advancement iPS cells technology can lead to the future success of reproductive medicine.
Fulltext Affordable ART for developing countries: a cost benefit comparison of low dose stimulation versus high dose GnRH antagonist protocol

Noorashikin M, Ong FB, Omar MH, Zainul-Rashid MR, Murad AZ, Shamsir A, et al.

J Assist Reprod Genet, 2008 Jul;25(7):297-303.
PMID: 18654847 DOI: 10.1007/s10815-008-9239-9

Low dose stimulation (LS) is emerging as an alternative regime in assisted reproductive technology (ART). This study aimed to compare the cost-effectiveness of LS to the high dose GnRH antagonist (Atg) regime.
Fulltext Epigenetic modification does not determine the time of POU5F1 transcription activation in cloned bovine embryos

Jafari S, Hosseini SM, Hajian M, Forouzanfar M, Jafarpour F, Abedi P, et al.

J Assist Reprod Genet, 2011 Nov;28(11):1119-27.
PMID: 22020531 DOI: 10.1007/s10815-011-9638-1

To investigate the effect of epigenetic modification on pattern, time and capacity of transcription activation of POU5F1, the key marker of pluripotency, in cloned bovine embryos.
Fulltext Singapore needs to update regulation of frozen egg donation after permitting social egg freezing

Chin AHB

J Assist Reprod Genet, 2022 Jul;39(7):1497-1500.
PMID: 35653043 DOI: 10.1007/s10815-022-02526-9

With social egg freezing being permitted in Singapore, there is expected to be an accumulated surplus of unused frozen eggs (vitrified oocytes) available for donation in coming years. A comprehensive update of current healthcare regulations pertaining to frozen egg donation is needed to resolve various pertinent ethical issues. In particular, the issue of egg donor anonymity should be addressed, together with the lack of sharing of medical and family information about the donor to prospective recipient patients and donor-conceived offspring. Rigorous and comprehensive genetic testing of prospective egg donors must be mandated to protect the welfare of recipient patients. Older women above 35 years of age should be required to have at least one child, before being allowed to donate their unused frozen eggs, to prevent any future regret and psychological problems of remaining childless, while being unsure of whether they have an unknown genetic offspring out there. New regulations drafted to address these ethical issues must also prevent potential conflicts of interests. For example, fertility doctors soliciting and encouraging former patients to donate their unused frozen eggs face an obvious conflict of interest, because additional medical fees will be earned by performing the egg donation procedure on other patients. A centralized donor registry should be established by the Singapore government to oversee the distribution and allocation of donated unused frozen eggs to infertile IVF patients. Such a registry could also facilitate sharing of vital health information about the donor to recipient patients and donor-conceived offspring.
Fulltext The probable destructive mechanisms behind COVID-19 on male reproduction system and fertility

Moshrefi M, Ghasemi-Esmailabad S, Ali J, Findikli N, Mangoli E, Khalili MA

J Assist Reprod Genet, 2021 Jul;38(7):1691-1708.
PMID: 33977466 DOI: 10.1007/s10815-021-02097-1

PURPOSE: The present study aims to summarize the current understanding of probable mechanisms and claims of adverse effects of SARS-CoV-2 on male fertility potential.
METHODS: Our search was including original articles, reviews, guidelines, letters to the editor, comments on guidelines, and editorials, regarding the male reproductive system. We used the words SARS-CoV-2, coronavirus, severe acute respiratory syndrome coronavirus 2, "2019 ncov," testis, sperm, male factor infertility, fertility treatment, semen, assisted reproductive technology (ART), sexual transmission, and ACE2.
RESULTS: Data showed coronavirus affects men more than women because of more expression of 2019 nCoV receptors (ACE2 and TMPRSS2) in testicular cells. Also, "Bioinformatics Analysis" suggests that sperm production may be damaged, since "Pseudo Time Analysis" has shown disruption in spermatogenesis. "Gene Ontology" (GO) showed an increase in viral reproduction and a decrease in sperm production-related terms. Recently, SARS-COV-2 mRNA and protein were detected in the semen of patients that had recovered from SARS-CoV-2 infection. Therefore, the probable disruption of blood-testis barrier (BTB) in febrile diseases is suspected in the acute phase of the disease enabling viral entry into the testes. Not only is spermatogenesis disturbed, but also disturbs gonadotropin, androgens, and testosterone secretion during SARS-CoV-2 infection. No sexual transmission has been reported yet; however, detection of the virus in semen still makes the sexual transmission an open question.
CONCLUSION: There is a concern that male fertility may be disturbed after the SARS-CoV-2 infection. Therefore, follow-up of the reproductive functions and male fertility may be necessary in recovered cases, especially in aged men.
Stringent criteria needed for germline genome editing of human IVF embryos

Chin AHB, Nguma JB, Ahmad MF

J Assist Reprod Genet, 2024 Jul;41(7):1727-1731.
PMID: 38695986 DOI: 10.1007/s10815-024-03125-6

Germline genome editing of IVF embryos is controversial because it is not directly health or lifesaving but is intended to prevent genetic diseases in yet-unborn future offspring. The following criteria are thus proposed for future clinical trials: (i) Due to medical risks, there should be cautious and judicious application while avoiding any non-essential usage, with rigorous patient counseling. (ii) Genome editing should only be performed on the entire batch of IVF embryos without initial PGT screening if all of them are expected to be affected by genetic disease. (iii) When there is a fair chance that some IVF embryos will not be affected by genetic diseases, initial PGT screening must be performed to identify unaffected embryos for transfer. (iv) IVF embryos with carrier status should not undergo germline genome editing. (v) If patients fail to conceive after the transfer of unaffected embryos, they should undergo another fresh IVF cycle rather than opt for genome editing of their remaining affected embryos. (vi) Only if the patient is unable to produce any more unaffected embryos in a fresh IVF cycle due to advanced maternal age or diminished ovarian reserves, can the genome editing of remaining affected embryos be permitted as a last resort.