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Erythropoietin (EPO) is the main mediator of erythropoiesis and an important tissue protective hormone that appears to mediate an ancestral neuroprotective innate immune response mechanism at an early age. When the young brain is threatened-prematurity, neonatal hyperbilirubinemia, malaria- EPO is hyper-secreted disproportionately to any concurrent anemic stimuli. Under eons of severe malarial selection pressure, neuroprotective EPO augmenting genetic determinants such as the various hemoglobinopathies, and the angiotensin converting enzyme (ACE) I/D polymorphism, have been positively selected. When malarial and other cerebral threats abate and the young child survives to adulthood, EPO subsides. Sustained high ACE and angiotensin II (Ang II) levels through the ACE D allele in adulthood may then become detrimental as witnessed by epidemiological studies. The ubiquitous renin angiotensin system (RAS) influences the α-klotho/fibroblast growth factor 23 (FGF23) circuitry, and both are interconnected with EPO. Here we propose that at a young age, EPO augmenting genetic determinants through ACE D allele elevated Ang II levels in some or HbE/beta thalassemia in others would increase EPO levels and shield against coronavirus disease 2019, akin to protection from malaria and dengue fever. Human evolution may use ACE2 as a “bait” for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to gain cellular entry in order to trigger an ACE/ACE2 imbalance and stimulate EPO hypersecretion using tissue RAS, uncoupled from hemoglobin levels. In subjects without EPO augmenting genetic determinants at any age, ACE2 binding and internalization upon SARS-CoV-2 entry would trigger an ACE/ACE2 imbalance, and Ang II oversecretion leading to protective EPO stimulation. In children, low nasal ACE2 Levels would beneficially augment this imbalance, especially for those without protective genetic determinants. On the other hand, in predisposed adults with the ACE D allele, ACE/ACE2 imbalance, may lead to uncontrolled RAS overactivity and an Ang II induced proinflammatory state and immune dysregulation, with interleukin 6 (IL-6), plasminogen activator inhibitor, and FGF23 elevations. IL-6 induced EPO suppression, aggravated through co-morbidities such as hypertension, diabetes, obesity, and RAS pharmacological interventions may potentially lead to acute respiratory distress syndrome, cytokine storm and/or autoimmunity. HbE/beta thalassemia carriers would enjoy protection at any age as their EPO stimulation is uncoupled from the RAS system. The timely use of rhEPO, EPO analogs, acetylsalicylic acid, bioactive lipids, or FGF23 antagonists in genetically predisposed individuals may counteract those detrimental effects.

Background and Methods. In Southeast Asia and particularly in Thailand, β0-thalassemia/hemoglobin E (HbE) disease is a common hereditary hematological disease. In a retrospective analysis, we investigated the outcomes of blastocyst preimplantation genetic diagnosis (PGD) for α- and β-thalassemia exclusion, with human leukocyte antigen (PGD-HLA) matching, from 2007 to 2016 at Superior A.R.T. (Bangkok, Thailand) and subsequent hematopoietic stem cell transplantation (HSCT) treatment of affected siblings. The main outcome measures included the proportion of biopsied cycles with at least one screened embryo suitable for transfer, implantation rate, live birth rate, and curative HSCT post-PGD-HLA. Results. In 221 cycles from 138 patients (104 cycles requiring HLA matching), 90.5% had embryo(s) biopsied for genetic testing. There were 119 embryo transfers for thalassemia (76) and thalassemia-HLA cases (43), respectively, resulting in overall clinical pregnancy rates of 54.6%, implantation rates of 45.7%, and live birth rates of 44.1%. Our dataset included fifteen PGD-HLA live births with successful HSCT in twelve affected siblings, 67% using umbilical cord blood stem cells (UCBSC) as the only SC source. Conclusions. We report favorable thalassemia PGD and PGD-HLA laboratory and clinical outcomes from a single center. The ultimate success in PGD-HLA is of course the cure of a thalassemia-affected sibling by HSCT. Our PGD-HLA HSCT series is the first and largest performed entirely in Asia with twelve successful and two pending cures and predominant UCBSC use.

To review currently available literature on the association between imprinting disorders (Beckwith-Wiedemann syndrome [BWS], Angelman syndrome [AS] and retinoblastoma) and assisted reproductive technology (ART) in humans.Publications related to imprinting/epigenetic disorders including BWS, AS, and retinoblastoma with ART, as well as articles publishing outcome of ART, including IVF and ICSI from July 1978 to February 2008, were identified using PubMed, Medline, and EMBASE.Considerable evidence in animal studies has demonstrated alteration in gene imprinting of embryos cultured in vitro. Publications from Europe, the United States, and Australia have suggested an association between ART and BWS. Importantly, more than 90% of children with BWS that were born after ART had imprinting defects, compared with 40%-50% of children with BWS and conceived without ART. Moreover, there have been other reports suggesting an association between AS and ART. The majority of children with AS born after ART had an imprinting defect as the underlying etiology, specifically loss of methylation of the maternal allele. There was a single report suggesting an increased incidence of retinoblastoma in children conceived with ART.Because the absolute incidence of imprinting disorders is small (1:12,000 births), routine screening for imprinting disorders in children conceived by ART is not recommended. Additional large cohort studies of children born after ART are needed to determine whether there is a genuine association between ART and imprinting disorders.

Simultaneous or concomitant bilateral adnexal pathology is rare. But simultaneous tubal pregnancy and twisted ovarian cyst is even rarer. A 25-year-old woman, gravida 2, parity 0, presented with acute abdomen after 12 weeks of amenorrhea. Simultaneous right tubal pregnancy and twisted left ovarian cyst were intraoperatively diagnosed. Right salpingostomy and left salpingo-oophorectomy were performed. The follow-up serum beta-hCG was negative at the nineteenth postoperative day. She was well at discharge and throughout the 4-week follow-up period. Although simultaneous or concomitant bilateral adnexal pathology is uncommon, a careful assessment of both adnexa is mandatory especially in the cases with inconsistent site of symptom and pathology in order to avoid undiagnosed simultaneous pathologies that may be missed.

Intrauterine devices (IUDs) are a viable treatment option for immunocompromised women who need contraception or menses suppression. They may also be an alternative treatment for women who have a contraindication to estrogen use. A review of the literature on IUD use in this population is sparse, but currently available data suggest that immunocompromised women are not at greater risk of developing pelvic infections.

In recent years, the success of human oocyte cryopreservation has improved dramatically. Currently, there are a couple hundred babies born worldwide with the use of cryopreserved oocytes. The oocyte survival after freezing/thawing process is in the range of 70-95%, comparable to embryo cryopreservation, depending on techniques used. With the change of cryopreservation media to choline-base, the outcome of oocyte cryopreservation has shown to improve. Moreover, new freezing technique, vitrification, has been developed resulting in better survival outcome without the need of sophisticated equipment. Fertilization rate of cryopreserved oocytes with ICSI is approximately 70-90%, comparable to that of fresh oocytes. However, the pregnancy rate varies from 10-40%. The main reason of varying outcome is the difference in technique of cryopreservation. Clinically, oocyte cryopreservation can be applied to preserve fertility of female cancer survivors, to delay childbearing and to quarantine oocytes in oocyte donor program. Oocyte cryopreservation can also be performed as an alternative to embryo cryopreservation due to ethical consideration.

The development of techniques to prolong the window of fertility for women has the ability to meet the needs of future populations and their delay in childbearing. With current techniques of cryopreservation of embryos, oocytes, or ovarian tissue, prolongation of fertility with varying success is feasible. In the future, rejuvenation of aging oocytes will offer the opportunity for the aging women to achieve pregnancy with their own genetic offspring. Production of germ cells from embryonic stem cells is another alternative for patient with poor or depleted germ cells. Better understanding of the cause of infertility can be achieved with new techniques to evaluate the oocytes, spermatozoa, and embryos on molecular and genetic levels. With improved understanding of the etiology of infertility, treatment will be more effective. With the advance of new drugs and surgical equipment, treatment of infertility will become more convenient and effective.

To assess the embryo formation rate after electrical activation on failed-to-fertilize oocytes after intracytoplasmic sperm injection (ICSI).A prospective, randomized, experimental study was conducted in our research laboratory at the Reproductive Medicine Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, between January and September 2004. One hundred failed-to-fertilize oocytes after ICSI were randomly assigned by stratified allocation according to oocyte grading before ICSI. Fifty unfertilized oocytes were activated with 3 consecutive 40-/microsec pulses of 1.5 kV/cm direct electrical current in buffer solution. The other 50 unfertilized oocytes, composing the control group, were treated in same way but without electrical activation. The embryo formation rates between the groups were compared.Embryo formation rates in the electrically activated group were 80% as compared with 16% in the control group (p0.001).Failed-to-fertilize oocytes after ICSI seem to be able to resume embryonic development after electrical activation.