Intra‐follicular kisspeptin levels are related to oocyte maturation and gonadal hormones in patients who are undergoing assisted reproductive technology

Taniguchi, Yoshiaki; Kuwahara, Akira; Tachibana, Ayaka; Yano, Yumiko; Yano, Kiyohito; Yamamoto, Yuri; Yamasaki, Mikio; Iwasa, Takeshi; Hinokio, Kenji; Matsuzaki, Takashi; Irahara, Minoru

doi:10.1002/rmb2.12056

Cited by 19 publications

(19 citation statements)

References 29 publications

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“…Our study observed that serum KP levels increased from FS to OPU stages of ART, followed by a decrease in ET stage. The findings are consistent with the results of another study [ 13 ]. A Saudi study showed a significant increase in serum KP and E2 levels from the early follicular to the preovulatory and the luteal stage among normal menstruating female medical students [ 14 ].…”

Section: Discussionsupporting

confidence: 93%

“…Furthermore, at ovulation induction (OI) during ART, higher serum KP levels are known to be associated with a better pregnancy outcome [ 6 ]. Low serum KP levels in UI females [ 9 ], and significant correlation of FF-KP with E2 concentrations and follicular maturity in infertile females undergoing ICSI [ 13 ], show a link between serum and FF KP concentrations and estradiol with the success of ICSI.…”

Section: Introductionmentioning

confidence: 99%

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Impact of serum and follicular fluid kisspeptin and estradiol on oocyte maturity and endometrial thickness among unexplained infertile females during ICSI

et al. 2020

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Objective To relate serum and follicular fluid (FF) kisspeptin and estradiol levels in different stages of stimulation during Intracytoplasmic Sperm Injection (ICSI) with oocyte maturity and endometrial thickness among unexplained infertile females. Methods This cross-sectional study was carried out at the Australian Concept Infertility Medical Centre from March 2017 till March 2018. Fifty unexplained infertile females, booked for ICSI, were included in the study. Serum kisspeptin and estradiol were estimated by Enzyme-Linked Immunosorbent Assay in all four stages; 1: follicular stimulation, 2: ovulation induction, 3: oocyte pickup, and 4: embryo transfer. FF was aspirated during oocyte retrieval (stage 3) for the analysis of KP and estradiol. Pregnancy outcomes were categorized as non-pregnant, preclinical abortion, and clinical pregnancy. Results The age of the study subjects was 32.04 ± 2.29 (Mean±SD) years, with mean BMI of 28.51 ± 4.15 (Mean±SD) kg/m 2 . Mean serum kisspeptin and estradiol levels increased in all subjects as the stimulation proceeded stages 1–3; however, the mean dropped after retrieval of the oocytes (stage 4). Out of 27 female subjects who completed the cycle, 17 remained non-pregnant, 4 had preclinical abortion, and 6 acquired clinical pregnancy. The FF kisspeptin concentration was significantly higher than serum concentrations and positively correlated with serum and FF estradiol concentrations. FF-kisspeptin correlated with serum kisspeptin in Stage 3 (r = 0.930, p<0.001), maturity of oocyte (r = 0.511, p = 0.006) and endometrial thickness (r = 0.522, p = 0.005). Kisspeptin in stage 3 was also found to correlate with endometrial thickness (r = 0.527, p = 0.005) and with estradiol (r = 0.624, p = 0.001) independently. Conclusion Increase in serum and FF-kisspeptin and estradiol levels from stages 1 to 3, resulted in an optimum endometrial thickness, probability of fertilization of oocytes and chances of clinical pregnancy in Assisted Reproductive Techniques /ICSI cycles of unexplained infertile females.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Impact of serum and follicular fluid kisspeptin and estradiol on oocyte maturity and endometrial thickness among unexplained infertile females during ICSI

et al. 2020

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“…Similarly, Itskovitz et al ( 211 ) found that intrafollicular estradiol and progesterone levels were higher in follicles containing a mature oocyte. Interestingly, intrafollicular kisspeptin levels are higher than corresponding serum kisspeptin levels, and they correlate with follicular fluid estradiol levels and the number of mature oocytes retrieved ( 212 ). Haas et al ( 213 ) assessed alterations in expression of genes related to steroidogenesis in granulosa cells of 24 women who received either GnRHa or hCG triggering.…”

Section: Endocrine Requirements For Oocyte Maturation and Ovulationmentioning

confidence: 99%

Novel Concepts for Inducing Final Oocyte Maturation in In Vitro Fertilization Treatment

2018

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Infertility affects one in six of the population and increasingly couples require treatment with assisted reproductive techniques. In vitro fertilization (IVF) treatment is most commonly conducted using exogenous FSH to induce follicular growth and human chorionic gonadotropin (hCG) to induce final oocyte maturation. However, hCG may cause the potentially life-threatening iatrogenic complication “ovarian hyperstimulation syndrome” (OHSS), which can cause considerable morbidity and, rarely, even mortality in otherwise healthy women. The use of GnRH agonists (GnRHas) has been pioneered during the last two decades to provide a safer option to induce final oocyte maturation. More recently, the neuropeptide kisspeptin, a hypothalamic regulator of GnRH release, has been investigated as a novel inductor of oocyte maturation. The hormonal stimulus used to induce oocyte maturation has a major impact on the success (retrieval of oocytes and chance of implantation) and safety (risk of OHSS) of IVF treatment. This review aims to appraise experimental and clinical data of hormonal approaches used to induce final oocyte maturation by hCG, GnRHa, both GnRHa and hCG administered in combination, recombinant LH, or kisspeptin. We also examine evidence for the timing of administration of the inductor of final oocyte maturation in relationship to parameters of follicular growth and the subsequent interval to oocyte retrieval. In summary, we review data on the efficacy and safety of the major hormonal approaches used to induce final oocyte maturation in clinical practice, as well as some novel approaches that may offer fresh alternatives in future.

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“…37 Furthermore, intrafollicular kisspeptin levels correlate with the number of mature oocytes retrieved. 5 Owens and colleagues 38 examined the in vivo and in vitro actions of using kisspeptin-54 trigger on gene expression relating to ovarian reproductive function, steroidogenesis, and OHSS in granulosa lutein cells, compared with current triggers. 38 They observed that triggering oocyte maturation with kisspeptin-54 increased the expression of genes involved in ovarian steroidogenesis such as LH/hCG and FSH receptor, steroid acute regulatory (STAR) protein, aromatase, and estrogen receptors.…”

Section: Kisspeptin During In Vitro Fertilizationmentioning

confidence: 99%

“…The decapeptide NKB is encoded for by the TAC3 gene and activates the neurokinin 3 receptor (NK3R) encoded by the TAC3R gene. [5][6][7][8][9] Patients with NK3R mutations have reduced gonadotrophin-releasing hormone (GnRH) pulsatility with an increase in follicle-stimulating hormone (FSH) to luteinizing hormone (LH) ratio. 10 Patients with either TAC3 or TAC3R mutations were shown to remain responsive to exogenous kisspeptin administration, consistent with NKB exerting its action upstream of kisspeptin.…”

mentioning

confidence: 99%

Clinical Translational Studies of Kisspeptin and Neurokinin B

Hunjan

Abbara

2019

Semin Reprod Med

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Kisspeptin and neurokinin B (NKB) are hypothalamic neuropeptides that are vital for reproductive health. An absence of either kisspeptin or NKB signaling results in hypogonadotrophic hypogonadism and a failure to proceed through puberty. In recent years, several studies have demonstrated potential avenues for the clinical utility of medications that act through these pathways in the assessment and treatment of reproductive disorders. Kisspeptin acts to stimulate hypothalamic gonadotrophic-releasing hormone (GnRH) secretion from the hypothalamus. Kisspeptin induces gonadotrophin secretion in both healthy men and women, and in women with reproductive disorders such as hypothalamic amenorrhea (HA). Kisspeptin-based treatments hold promise for use during in vitro fertilization (IVF) treatment; a bolus of kisspeptin-54 induces an LH surge of 12 to 14 hours of duration sufficient to induce oocyte maturation, but with markedly reduced rates of the most significant complication of IVF treatment, ovarian hyperstimulation syndrome (OHSS). Kisspeptin could also be used chronically to restore reproductive health in patients with functional hypogonadism, such as those with HA. Furthermore, kisspeptin has potential as a diagnostic test of hypothalamic function; a “kisspeptin test” could be used in children with delayed puberty to identify the subset with genetically determined deficits in hypothalamic pathways (congenital hypogonadotrophic hypogonadism [CHH]). In addition to its role in hypothalamic GnRH pulse generation, NKB plays a critical role in the occurrence of one of the most troubling symptoms of the menopause, the “hot flush.” Neurokinin-3 receptor (NK3R) antagonists are highly effective as treatments for hot flushes in postmenopausal women, with several compounds now in late-phase development. Furthermore, NK3R antagonism leads to a reduction in LH secretion by reducing GnRH pulsatility in the hypothalamus and has been shown to reduce androgen levels in women with polycystic ovary syndrome (PCOS) (in whom GnRH pulsatility is often increased). In summary, although further detailed evaluation in several clinical settings is ongoing, medications based on kisspeptin and NKB pathways have prodigious potential in the assessment and treatment of reproductive disorders.

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Intra‐follicular kisspeptin levels are related to oocyte maturation and gonadal hormones in patients who are undergoing assisted reproductive technology

Cited by 19 publications

References 29 publications

Impact of serum and follicular fluid kisspeptin and estradiol on oocyte maturity and endometrial thickness among unexplained infertile females during ICSI

Impact of serum and follicular fluid kisspeptin and estradiol on oocyte maturity and endometrial thickness among unexplained infertile females during ICSI

Novel Concepts for Inducing Final Oocyte Maturation in In Vitro Fertilization Treatment

Clinical Translational Studies of Kisspeptin and Neurokinin B

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