Two consecutive pregnancies in a patient with premature ovarian insufficiency in the course of classic galactosemia and a review of the literature

Kruszewska, Jagoda; Laudy-Wiaderny, Hanna; Krzywdzińska, Sandra; Grymowicz, Monika; Smolarczyk, Roman; Męczekalski, Błażej

doi:10.1080/09513590.2021.1998437

Cited by 7 publications

(2 citation statements)

References 40 publications

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“…In addition, Spencer et al (2013) demonstrated three other clinical modifiers for the severity of ovarian dysfunction in CG, namely low levels of AMH, elevated levels of FSH and a low AFC. However, a spontaneous pregnancy in a woman with CG and a prediction of no ovarian reserve and undetectable AMH levels has been reported ( Gubbels et al , 2009 ; Kruszewska et al , 2022 ). Elevated levels of FSH and low levels of AMH indicate POI and significantly impaired ovarian reserve, but do not rule out the possibility of scattered small, quiescent follicles.…”

Section: Spontaneous Pregnanciesmentioning

confidence: 99%

The hypergonadotropic hypogonadism conundrum of classic galactosemia

Derks

Rivera-Cruz

Hagen-Lillevik

et al. 2022

Human Reproduction Update

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BACKGROUND Hypergonadotropic hypogonadism is a burdensome complication of classic galactosemia (CG), an inborn error of galactose metabolism that invariably affects female patients. Since its recognition in 1979, data have become available regarding the clinical spectrum, and the impact on fertility. Many women have been counseled for infertility and the majority never try to conceive, yet spontaneous pregnancies can occur. Onset and mechanism of damage have not been elucidated, yet new insights at the molecular level are becoming available that might greatly benefit our understanding. Fertility preservation options have expanded, and treatments to mitigate this complication either by directly rescuing the metabolic defect or by influencing the cascade of events are being explored. OBJECTIVE AND RATIONALE The aims are to review: the clinical picture and the need to revisit the counseling paradigm; insights into the onset and mechanism of damage at the molecular level; and current treatments to mitigate ovarian damage. SEARCH METHODS In addition to the work on this topic by the authors, the PubMed database has been used to search for peer-reviewed articles and reviews using the following terms: ‘classic galactosemia’, ‘gonadal damage’, ‘primary ovarian insufficiency’, ‘fertility’, ‘animal models’ and ‘fertility preservation’ in combination with other keywords related to the subject area. All relevant publications until August 2022 have been critically evaluated and reviewed. OUTCOMES A diagnosis of premature ovarian insufficiency (POI) results in a significant psychological burden with a high incidence of depression and anxiety that urges adequate counseling at an early stage, appropriate treatment and timely discussion of fertility preservation options. The cause of POI in CG is unknown, but evidence exists of dysregulation in pathways crucial for folliculogenesis such as phosphatidylinositol 3-kinase/protein kinase B, inositol pathway, mitogen-activated protein kinase, insulin-like growth factor-1 and transforming growth factor-beta signaling. Recent findings from the GalT gene-trapped (GalTKO) mouse model suggest that early molecular changes in 1-month-old ovaries elicit an accelerated growth activation and burnout of primordial follicles, resembling the progressive ovarian failure seen in patients. Although data on safety and efficacy outcomes are still limited, ovarian tissue cryopreservation can be a fertility preservation option. Treatments to overcome the genetic defect, for example nucleic acid therapy such as mRNA or gene therapy, or that influence the cascade of events are being explored at the (pre-)clinical level. WIDER IMPLICATIONS Elucidation of the molecular pathways underlying POI of any origin can greatly advance our insight into the pathogenesis and open new treatment avenues. Alterations in these molecular pathways might serve as markers of disease progression and efficiency of new treatment options.

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Section: Spontaneous Pregnanciesmentioning

confidence: 99%

The hypergonadotropic hypogonadism conundrum of classic galactosemia

Derks

Rivera-Cruz

Hagen-Lillevik

et al. 2022

Human Reproduction Update

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“…Galactosemia is an inherited disorder due to an enzymatic defect in galactose metabolism to glucose (Flechtner et al, 2021; van Erven et al, 2017). Toxicity of galactose accumulated in the body leads to premature ovarian failure in women (Kruszewska et al, 2022). In the absence of enzyme deficiency, experimental induction of galactosemia during embryonic development in rats resulted in poor ovarian reserve (Bandyopadhyay et al, 2003; Chen et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Continued exposure to D‐galactose in postnatal period may inhibit excessive primordial follicle reduction in rats exposed prenatally to D‐galactose

Dovom

Noroozzadeh

Mosaffa

et al. 2022

Birth Defects Research

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We aimed to compare the ovarian reserve of rats exposed to oral D‐galactose during prenatal and early life with rats exposed to D‐galactose only during the prenatal period. Fifteen female pregnant Wistar rats were randomly divided into three groups. The first and second groups were fed a D‐galactose enriched diet (35%) from the third day of pregnancy to parturition (PP) and the third day to the end of lactation (PL), respectively. The control group (C group) was fed a standard diet. The study population was the female offspring of three groups (PP′, PL′, and C′), in which some reproductive factors were examined between 45 and 50 days of age. When compared with the PP′ group, the number of primordial follicles was significantly higher in the PL′ group at PND 45–50 (40 vs. 30; p = .01); however, the antimullerian hormone level was significantly reduced in the PL′ group versus control group (−2.2, 95% confidence interval [CI]: −2.83, −1.53 ng/ml p = .000), and follicle‐stimulating hormone level significantly increased in PP′ group versus control (4.5 mIU/ml, 95% CI: 1.40–7.62, p = .005). There was no significant difference in leukocyte infiltration or antiovarian antibody among the groups. Continued exposure to D‐galactose during the lactation period inhibits the primordial follicle loss in rats in terms of producing fewer atretic follicles.

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Inborn errors of metabolism and pregnancy

Murphey,

Krishna,

2024

American Journal of Obstetrics & Gynecology MFM

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Two consecutive pregnancies in a patient with premature ovarian insufficiency in the course of classic galactosemia and a review of the literature

Cited by 7 publications

References 40 publications

The hypergonadotropic hypogonadism conundrum of classic galactosemia

The hypergonadotropic hypogonadism conundrum of classic galactosemia

Continued exposure to D‐galactose in postnatal period may inhibit excessive primordial follicle reduction in rats exposed prenatally to D‐galactose

Inborn errors of metabolism and pregnancy

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