research paper 2

Citation

Conceptual Framework

Design/Method

Sample/setting

Major variables

Measurement

Data analysis

Findings

Appraisal

Murray, A.,Schoemaker, M.J., Bennett, C.E., Ennis, S., Macpherson, J. N., Jones, M. …Swerdlow, A.J. (2014). Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency. Genetics in Medicine, 16(1), 19–24. http://doi.org/10.1038/gim.2013.64

Inthe absence of a population-based estimate, assessing the effect of premutationincidence and intermediate alleles is difficult in POI over the reproductive life span.

The study determined the prevalence of premutation and the intermediate alleles in women with primary ovarian insufficiency and early menopause.

Population of more than 2,000 women was sampled from the Breakthrough Generations for individuals who underwent menopause earlier than 46 years of age.

CGG repeat length

Age at natural menopause

It applied the polymorphic CGG trinucleotide repeats

The study used STATAv12 for logistic and linear regression analysis to test the association between CGG repeat length and age at natural menopause

All expanded premutation-sized alleles observed in controls were <66 repeats.

The larger premutation alleles (>65 repeats) were all in women with either EM or POI

FMR1premutations may are notthe most common cause of ovarian failure as previously estimated, but they are still significant cause of ovarian failure.

Le QuesneStabej, P., Williams, H. J., James, C., Tekman, M., Stanescu, H. C., Kleta, R., …GOSgene. (2016). STAG3 truncating variant as the cause of primary ovarian insufficiency. European Journal of Human Genetics, 24(1), 135–138. http://doi.org/10.1038/ejhg.2015.107

POI is heterogeneous with a few causative genes discovered so far

This was a multipoint parametric linkage study on the HumanCytoSNP-12v2-1_H Beadarray

Study involved five family members: two affected sisters, and an unaffected sister

Complete penetrance

Disease allele frequency

Multipoint parametric linkage analysis

Whole-exome sequencing was done on the proband.

Linkage analysis identified a locus on chromosome 7

Variant annotation and interpretation analyses using the Ingenuity Variant Analysis software version 3.0.20140422

A multipoint parametric linkage analysisshowed five linked regions on chromosomes 2, 5, 7 and 16.

They also revealed a logarithm of odds (LOD) score for a consanguineous pedigree matching the one expected of 1.93

There is potential for involvement of other meiosis-specific genes in the cohesin complex associated with POI pathogenesis

Nao, S.,Nobuhito, Y., Seido, T.,Yodo, S.,Midori, T., …Kazuhiro, K. (2015).Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Human Reproduction, 30(3). Pp. 608–615https://doi.org/10.1093/humrep/deu353

Vitrificationapproach preceding IVA treatment is a potential therapy for infertility in POI patients with ovaries containing residual follicles

Clinicalstudy involving laparoscopic surgery, ovariectomy

The study also monitored Follicle growth was trough ultrasound and serum estrogen levels

Involved 37 infertile women with POI. The patients had had a shorter duration of amenorrhea

Follicle growth

Serum estrogen levels

Non-parametric Kruskal–Wallis test was used in evaluating the differences of time from the Follicle growth was of diagnosis of POI to ovariectomy

Fisher's exact test was used in analysis of proportion of patients with endometriosis.

Numbers of ovarian strips from POI patients were limited compared with those in ‘normal’ ovaries in cancer patients, in which,

POI: mean 7.2 ± 5.4 strips, range: 1.5–25 per ovary, n = 37

Cancer patient: mean 19.2 ± 5.1 strips, range: 11–30 per ovary, n = 18).

The present approach was a representation of success in cryopreservation of ovarian tissues through vitrificationto generate functional mature oocytes for treating infertility.

Chemaitilly, W., et al. (2017). Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort. The Journal of Clinical Endocrinology & Metabolism, 102(7). Pp. 2242–2250, https://doi.org/10.1210/jc.2016-3723

Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited.

Cross-sectional Study at the St. Jude Lifetime Cohort

Nine hundred twenty-one participants of median age of 31.7 years were evaluated at a median of 24.0 years following cancer diagnosis

Prevalence of POI

Risk factors

Long-term adverse health outcomes

Multivariable Cox regression for studyingthe association between treatment-related risk factors and POI.

Multivariable logistic regression analysed the associations between POI and markers for cardiovascular disease, bone mineral density (BMD), and frailty.

Prevalence of POI was estimated at 10.9%. Patients with a BMI ≥30 kg/m2 at the time of the Cohort assessment had less likelihood of POI diagnosis.

A low BMD and frailty are independently associated with POI.

Norling, A., et al. (2014).Identification of a duplication within the GDF9 gene and novel candidate genes for primary ovarian insufficiency (POI) by a customized high-resolution array comparative genomic hybridization platform.

Human Reproduction, 29(8). Pp. 1818–1827. https://doi.org/10.1093/humrep/deu149

Mutation that affects regulatory regions of growth differentiation factor 9 (GDF9) are associated with novel candidate genes for POI.

This was a case–control study

95 controls were used together with an additional population 28 patients with POI over a 1-year period

Genes in sex development

GDF9 gene duplication

Multiplex ligation-dependent probe amplification (MLPA) probe

PCR amplification and sequencing model

Identified 11 unique copy number changes in 11 patients, including tandem duplication of 475 bp, with part of GDF9 gene promoter region.

The duplicated region having three NOBOX-binding elements and E-box are important elements for regulation of GDF9 gene.