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1.
Reprod Toxicol ; 108: 56-61, 2022 03.
Article in English | MEDLINE | ID: covidwho-1720799

ABSTRACT

Nirmatrelvir (PF-07321332; NMV) the antiviral component of PAXLOVID™ is a potent and selective inhibitor of the SARS-CoV-2 main protease (Mpro), which plays a critical role in viral replication. PAXLOVID, comprised of nirmatrelvir and ritonavir (used as a pharmacokinetic enhancer), is an oral therapy currently in development as a therapeutic option for those infected with SARS-CoV-2 to prevent progression to severe disease, hospitalization, and death. PAXLOVID has been shown to be efficacious against hospitalization and death in two Phase 2/3 clinical studies that evaluated non hospitalized patients both with and without high risk factors for progression to severe illness. Given that males and females of reproductive age are included in the intended patient population, we assessed the potential effects of NMV up to the limit dose of 1000 mg/kg/day in ICH guideline embryo-fetal development studies in rats and rabbits, and a fertility and early embryonic development study in rats. There were no effects on male and female fertility or early embryonic development in rats, and no severe manifestations of developmental toxicity in rats or rabbits. The lack of adverse findings reported here in nonclinical species is consistent with the intended therapeutic target of NMV (a virus specific protein not present in mammalian cells), the favorable off-target selectivity profile, and lack of genetic toxicity. The results of these nonclinical studies with NMV along with existing ritonavir safety information indicate that there are no clinically relevant risks associated with PAXLOVID administration during pregnancy and in males and females of reproductive age.


Subject(s)
Antiviral Agents/toxicity , COVID-19/drug therapy , Embryonic Development/drug effects , Fertility/drug effects , Lactams/toxicity , Leucine/toxicity , Nitriles/toxicity , Proline/toxicity , Ritonavir/toxicity , Animals , Drug Combinations , Female , Infertility/chemically induced , Male , Pregnancy , Rabbits , Rats , Rats, Wistar
2.
Reprod Toxicol ; 107: 69-80, 2022 01.
Article in English | MEDLINE | ID: covidwho-1531737

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted tens of millions of people in a worldwide pandemic. A recently developed recombinant Plant-Derived Virus-Like Particle Vaccine candidate for COVID-19 (CoVLP) formulated with AS03 has been shown to be well-tolerated and highly immunogenic in healthy adults. Since the target population for the vaccine includes women of childbearing potential, the objective of the study was to evaluate any untoward prenatal and postnatal effects of AS03-adjuvanted CoVLP administered intramuscularly to Sprague-Dawley female rats before cohabitation for mating (22 and 8 days prior) and during gestation (Gestation Days [GD] 6 and 19). The embryo-fetal development (EFD) cohort was subjected to cesarean on GD 21 and the pre/post-natal (PPN) cohort was allowed to naturally deliver. Effects of AS03-adjuvanted CoVLP was evaluated on pregnant rats, embryo-fetal development (EFD), during parturition, lactation and the development of the F1 offspring up to weaning Vaccination with AS03-adjuvanted CoVLP induced an antibody response in F0 females and anti-SARS-CoV-2 spike-specific maternal antibodies were detected in the offspring at the end of the gestation and lactation periods. Overall, there was no evidence of untoward effects of AS03-adjuvanted CoVLP on the fertility or reproductive performance of the vaccinated F0 females. There was no evidence of untoward effects on embryo-fetal development (including teratogenicity), or early (pre-weaning) development of the F1 offspring. These results support the acceptable safety profile of the AS03-adjuvanted CoVLP vaccine for administration to women of childbearing potential.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Embryonic Development/drug effects , Fertility/drug effects , Fetal Development/drug effects , Polysorbates/administration & dosage , Squalene/administration & dosage , Vaccines, Virus-Like Particle/administration & dosage , alpha-Tocopherol/administration & dosage , Animals , Animals, Newborn , Antibodies, Viral/blood , Drug Combinations , Female , Immunoglobulin G/blood , Maternal-Fetal Exchange , Pregnancy , Rats, Sprague-Dawley , Recombinant Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Tobacco/genetics
3.
Reprod Biomed Online ; 44(1): 145-149, 2022 01.
Article in English | MEDLINE | ID: covidwho-1447086

ABSTRACT

RESEARCH QUESTION: Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters? DESIGN: A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1-2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology. RESULTS: The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 â€¯×  106/ml, with only a single participant (1.3%) with a sperm count of 12.5 â€¯×  106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO. CONCLUSIONS: The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.


Subject(s)
BNT162 Vaccine/adverse effects , Fertility/drug effects , Semen Analysis , Adult , Humans , Male , Middle Aged , Prospective Studies
4.
J Reprod Immunol ; 148: 103428, 2021 11.
Article in English | MEDLINE | ID: covidwho-1433588

ABSTRACT

This opinion paper briefly presents arguments that support the unlikelihood of an impact on female fertility from current covid-19 vaccines.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Fertility/drug effects , Vaccination/adverse effects , Female , Humans
6.
Basic Clin Pharmacol Toxicol ; 128(5): 635-641, 2021 May.
Article in English | MEDLINE | ID: covidwho-1132864

ABSTRACT

Opioids cover a broad class of natural, synthetic and semi-synthetic drugs that act on opioid receptors to produce powerful analgesic effects. Rates of opioid use and opioid agonist maintenance treatment have increased substantially in recent years, particularly among women. Trends and outcomes of opioids use on fertility, pregnancy and breastfeeding, and longer-term child developmental outcomes have not been well-described. Here, we review the existing literature on the health effects of opioid use on female fertility, pregnancy, breastmilk and the exposed infant. We find that the current literature is primarily concentrated on the impact of opioid use in pregnancy and neonatal outcomes, with little exploration of effects on fertility. Studies are limited in number, some with small sample sizes, and many are hampered by methodological challenges related to confounding and other potential biases. Opioid use is becoming more prevalent due to environmental pressures such as COVID-19. More research is needed to better elucidate its effects on reproductive health among younger women and support the development of evidence-based recommendations for safe prescription practices and public health messaging.


Subject(s)
Breast Feeding , Fertility/drug effects , Opioid-Related Disorders , Practice Patterns, Physicians' , Pregnancy Complications , COVID-19/epidemiology , Female , Humans , Infant, Newborn , Opioid-Related Disorders/complications , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/prevention & control , Practice Patterns, Physicians'/standards , Practice Patterns, Physicians'/trends , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Complications/prevention & control , Prevalence , SARS-CoV-2
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