Gonadotropins as pharmacological agents in assisted reproductive technology and polycystic ovary syndrome

Singh, Rita; Kaur, Surleen; Yadav, Suman; Bhatia, Smita

doi:10.1016/j.tem.2023.02.002

Cited by 10 publications

(6 citation statements)

References 149 publications

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“…These schemes used for ovulation induction include the addition of adjuvant therapy, increased gonadotropin dosages, and different procedures for pituitary suppression during ovarian stimulation (37)(38)(39). However, high doses of gonadotrophins are often associated with a range of unexpected side effects (40). Hence, exploring an optimal adjuvant treatment remains an ongoing clinical challenge.…”

Section: Discussionmentioning

confidence: 99%

Clinical evidence of growth hormone for infertile women with diminished ovarian reserve undergoing IVF: a systematic review and meta-analysis

Lin,

Zhong,

et al. 2023

Front. Endocrinol.

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ObjectiveTo appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF).MethodsRelevant RCTs published in Chinese or English were identified through a comprehensive search of nine databases from the period of database inception to April 20, 2023. We included trials investigating adjuvant GH during ovarian stimulation and reported the subsequent outcomes. The group with adjuvant GH treatment and the group without adjuvant GH treatment were set up as the trial and control groups, respectively. The quality of RCTs was measured according to the Cochrane Collaboration Handbook.ResultsOf the 579 studies initially identified, 10 RCTs comprising 852 infertile women with DOR were included. The GH dose of individual trials ranged between 3 and 5 IU/day. Overall, we judged the trials to be at high risk of bias in the blinding domain. Pooled results showed that GH was associated with an increased clinical pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], p < 0.0001) and a greater number of oocytes retrieved (MD = 0.91, 95%CI [0.47, 1.35], p < 0.0001). Favorable associations were also observed when ovarian stimulation was combined with GH therapy for improving the optimal embryos rate (RR = 1.84, 95%CI [1.30, 2.59], p = 0.0005) and the number of optimal embryos (MD = 0.28, 95%CI [0.08, 0.48], p = 0.005) along with reducing the cycle cancellation rate (RR = 0.46, 95%CI [0.24, 0.89], p = 0.02). Moreover, GH resulted in an increase in the fertilization rate (RR = 1.33, 95%CI [1.18, 1.50], p < 0.00001) and the embryo implantation rate (RR = 1.56, 95%CI [1.21, 2.01], p = 0.0006). In addition, there was a significant enhancement in estradiol levels (SMD = 1.18, 95%CI [0.46, 1.91], p = 0.001) and endometrial thickness (MD = 0.75, 95%CI [0.41, 1.09], p < 0.0001) on the day of hCG. With regard to the total number of days and total dose of gonadotrophins used, GH treatment was correlated with shorter days (MD = -0.26, 95%CI [-0.46, -0.06], p = 0.01) and lower dose (MD = -460.97, 95%CI [-617.20, -304.73], p < 0.00001) of gonadotrophins applied during ovarian stimulation. Furthermore, GH in conjunction with the GnRH antagonist protocol was more conducive to improving the number of oocytes retrieved when compared with the GnRH agonist protocol (p < 0.0001). Moreover, a notable association was also seen in IVF combined with GH more than or equal to 4.5 IU/day to increase the number of optimal embryos and estradiol levels on the day of hCG (p < 0.05).ConclusionFor infertile women with DOR undergoing IVF, adjuvant treatment with GH during ovarian stimulation protocols showed better clinical outcomes, shorter days and lower dosages of gonadotrophin required. Furthermore, well-designed RCTs are needed to verify our results in the future.Systematic review registrationhttps://www.crd.york.ac.uk PROSPERO (CRD42023421739)

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Section: Discussionmentioning

confidence: 99%

Clinical evidence of growth hormone for infertile women with diminished ovarian reserve undergoing IVF: a systematic review and meta-analysis

Lin,

Zhong,

et al. 2023

Front. Endocrinol.

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“…Polycystic ovary syndrome (PCOS) is a common condition affecting the female reproductive system. It can cause infertility and complications during pregnancy, and affects the physical and mental health of 4%-20% of women of reproductive age globally ( 82 , 83 ). The main clinical manifestations of PCOS include irregular menstruation (hypomenorrhea or amenorrhea), androgen excess, and multiple ovarian cysts, often accompanied by insulin resistance (IR), obesity, type 2 diabetes, and cardiovascular disease ( 83 , 84 ).…”

Section: The Role Of Hmgb1 In Female Reproductive System Diseasesmentioning

confidence: 99%

HMGB1: a double-edged sword and therapeutic target in the female reproductive system

Ren,

Zhu,

Han

et al. 2023

Front. Immunol.

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HMGB1 that belongs to the High Mobility Group-box superfamily, is a nonhistone chromatin associated transcription factor. It is present in the nucleus of eukaryotes and can be actively secreted or passively released by kinds of cells. HMGB1 is important for maintaining DNA structure by binding to DNA and histones, protecting it from damage. It also regulates the interaction between histones and DNA, affecting chromatin packaging, and can influence gene expression by promoting nucleosome sliding. And as a DAMP, HMGB1 binding to RAGE and TLRs activates NF-κB, which triggers the expression of downstream genes like IL-18, IL-1β, and TNF-α. HMGB1 is known to be involved in numerous physiological and pathological processes. Recent studies have demonstrated the significance of HMGB1 as DAMPs in the female reproductive system. These findings have shed light on the potential role of HMGB1 in the pathogenesis of diseases in female reproductive system and the possibilities of HMGB1-targeted therapies for treating them. Such therapies can help reduce inflammation and metabolic dysfunction and alleviate the symptoms of reproductive system diseases. Overall, the identification of HMGB1 as a key player in disease of the female reproductive system represents a significant breakthrough in our understanding of these conditions and presents exciting opportunities for the development of novel therapies.

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“…PCOS is characterized by hyperandrogenism, anovulation, polycystic morphology of the ovary, and menstrual irregularities [1][2][3] [Figure 1]. One of the main endocrinological disturbances in women with PCOS is the increased levels of Luteinizing Hormone (LH), and consequently a high LH:FSH ratio [1][2][3][4][5] . Neuroendocrine defects in estrogen and progesterone feedback mechanisms lead to gonadotropin imbalance and hyperandrogenism in women 6 .…”

Section: Introductionmentioning

confidence: 99%

Adipose Tissue Dysfunction in PCOS

Aparupa,

Singh

2024

JER

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Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine diseases among women of reproductive age; however, its aetiology is unclear. PCOS is linked to many metabolic manifestations and alterations such as obesity, insulin resistance, and cardiovascular diseases (CVD). Women with PCOS have intra-ovarian and systemic changes in their metabolite levels. Adipose tissue dysfunction plays a significant role in the pathophysiology of PCOS. Adipose tissue growth is disrupted by metabolic stress, leading to hypertrophy of adipocytes, which begin to express stress signals. Adipose tissue secretes autocrine and paracrine factors, called adipokines or adipocytokines. Adiponectin is an adipocyte-derived protein abundant in the bloodstream. Plasma adiponectin concentration is low in women with PCOS, obesity, CVD, and hypertension. Other adipocytokines with altered secretion in PCOS include leptin, resistin, apelin, visfatin, IL-6, IL-8, and TNF-α. Hormonal imbalance, untimely action of high LH, and consequent hyperandrogenism in women with PCOS may cause metabolic defects associated with adipose tissue dysfunction; however, there are no reports on the role of higher LH levels in adipose dysfunction and altered adipokine secretion. New medications with therapeutic potential have been developed that target adipokines for the treatment of PCOS. This review discusses the association between PCOS and altered adipokine production as a consequence of adipose dysfunction.

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Gonadotropins as pharmacological agents in assisted reproductive technology and polycystic ovary syndrome

Cited by 10 publications

References 149 publications

Clinical evidence of growth hormone for infertile women with diminished ovarian reserve undergoing IVF: a systematic review and meta-analysis

Clinical evidence of growth hormone for infertile women with diminished ovarian reserve undergoing IVF: a systematic review and meta-analysis

HMGB1: a double-edged sword and therapeutic target in the female reproductive system

Adipose Tissue Dysfunction in PCOS

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