scholarly journals Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea

1999 ◽  
Vol 14 (12) ◽  
pp. 2963-2968 ◽  
Author(s):  
I.R. Pirwany ◽  
R.W.S. Yates ◽  
I.T. Cameron ◽  
R. Fleming
1999 ◽  
Vol 68 (2) ◽  
pp. 257-284 ◽  
Author(s):  
R. Webb ◽  
R. G. Gosden ◽  
E. E. Telfer ◽  
R. M. Moor

AbstractThis review addresses the reasons for the lack of progress in the control of superovulation and highlights the importance of understanding the mechanisms underlying follicular development. The present inability to provide large numbers of viable embryos from selected females still restricts genetic improvement, whilst variability in ovarian response to hormones limit the present capacity for increasing reproductive efficiency.Females are born with a large store of eggs which rapidly declines as puberty approaches. If these oocytes are normal then there is scope for increasing the reproductive potential of selected females. Oocytes must reach a certain size before they can complete all stages of development and the final changes that occur late in follicular development. It is likely that oocytes that do not produce specific factors at precise stages of development will not be viable. Hence, it is important to characterize oocyte secreted factors since there are potential indicators of oocyte quality.The mechanisms that determine ovulation rate have still not been fully elucidated. Indeed follicular atresia, the process whereby follicles regress, is still not known. A better understanding of these processes should prove pivotal for the synchronization of follicular growth, for more precise oestrous synchronization and improved superovulatory response.Nutrition can influence a whole range of reproductive parameters however, the pathways through which nutrition acts have not been fully elucidated. Metabolic hormones, particularly insulin and IGFs, appear to interact with gonadotrophins at the level of the gonads. Certainly gonadotropins provide the primary drive for the growth of follicles in the later stages of development and both insulin and IGF-1, possibly IGF-2, synergize with gonadotrophins to stimulate cell proliferation and hormone production. More research is required to determine the effects of other growth factors and their interaction with gonadotropins.There is evidence, particularly from studies with rodents, that steroids can also modulate follicular growth and development, although information is very limited for ruminants. There may be a rôle for oestrogens in synchronizing follicular waves, to aid in oestrous synchronization regimes and for removing the dominant follicle to achieve improved superovulatory responses. However more information is required to determine whether these are feasible approaches.Heritability for litter size is higher in sheep than in cattle. Exogenous gonadotropins are a commercially ineffective means of inducing twinning in sheep and cattle. Although there are differences in circulating gonadotropin concentrations, the mechanism(s) responsible for the high ovulation appear to reside essentially within the ovaries. The locus of the Booroola gene, a major gene for ovulation rate, has been established but not specifically identified. However sheep possessing major genes do provide extremely valuable models for investigating the mechanisms controlling ovulation rate, including a direct contrast to mono-ovulatory species such as cattle.In conclusion, the relationship between oocyte quality, in both healthy follicles and those follicles destined for atresia, must be resolved before the future potential for increasing embryo yield can be predicted. In addition, a greater understanding of the factors affecting folliculogenesis in ruminants should ensure that the full benefits ensuing from the precise control of ovarian function are achieved. The improved use of artificial insemination and embryo transfer that would ensue from a greater understanding of the processes of folliculo genesis, coupled with the new technologies of genome and linkage mapping, should ensure a more rapid rate of genetic gain.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 928
Author(s):  
Philippe Monget ◽  
Ken McNatty ◽  
Danielle Monniaux

From fetal life until senescence, the ovary is an extremely active tissue undergoing continuous structural and functional changes. These ever-changing events are best summarized by a quotation attributed to Plato when describing motion in space and time—‘nothing ever is but is always becoming…’. With respect to the ovary, these changes include, at the beginning, the processes of follicular formation and thereafter those of follicular growth and atresia, steroidogenesis, oocyte maturation, and decisions relating to the number of mature oocytes that are ovulated for fertilization and the role of the corpus luteum. The aims of this review are to offer some examples of these complex and hitherto processes. The ones herein have been elucidated from studies undertaken in vitro or from normal in vivo events, natural genetic mutations or after experimental inactivation of gene function. Specifically, this review offers insights concerning the initiation of follicular growth, pathologies relating to poly-ovular follicles, the consequences of premature loss of germ cells or oocytes loss, the roles of AMH (anti-Müllerian hormone) and BMP (bone morphogenetic protein) genes in regulating follicular growth and ovulation rate together with species differences in maintaining luteal function during pregnancy. Collectively, the evidence suggests that the oocyte is a key organizer of normal ovarian function. It has been shown to influence the phenotype of the adjacent somatic cells, the growth and maturation of the follicle, and to determine the ovulation rate. When germ cells or oocytes are lost prematurely, the ovary becomes disorganized and a wide range of pathologies may arise.


2011 ◽  
Vol 252 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Karina A. Barreiro ◽  
María P. Di Yorio ◽  
Romina D. Artillo-Guida ◽  
Dante A. Paz ◽  
Alicia G. Faletti

Author(s):  
Macarena B Gonzalez ◽  
Rebecca L Robker ◽  
Ryan D Rose

Abstract The prevalence of obesity in adults worldwide, and specifically in women of reproductive age, is concerning given the risks to fertility posed by the increased risk of type 2 diabetes, metabolic syndrome and other non-communicable diseases. Obesity has a multi-systemic impact in female physiology that is characterized by the presence of oxidative stress, lipotoxicity, and the activation of pro-inflammatory pathways, inducing tissue-specific insulin resistance and ultimately conducive to abnormal ovarian function. A higher body mass is linked to Polycystic Ovary Syndrome, dysregulated menstrual cycles, anovulation, and longer time to pregnancy, even in ovulatory women. In the context of ART, compared to women of normal BMI, obese women have worse outcomes in every step of their journey, resulting in reduced success measured as live birth rate. Even after pregnancy is achieved, obese women have a higher chance of miscarriage, gestational diabetes, pregnancy complications, birth defects, and most worryingly, a higher risk of stillbirth and neonatal death. The potential for compounding effects of ART on pregnancy complications and infant morbidities in obese women has not been studied. There is still much debate in the field on whether these poorer outcomes are mainly driven by defects in oocyte quality, abnormal embryo development or an unaccommodating uterine environment, however the clinical evidence to date suggests a combination of all three are responsible. Animal models of maternal obesity shed light on the mechanisms underlaying the effects of obesity on the peri-conception environment, with recent findings pointing to lipotoxicity in the ovarian environment as a key driver of defects in oocytes that have not only reduced developmental competence but long-lasting effects in offspring health.


1987 ◽  
Vol 64 (2) ◽  
pp. 507-516 ◽  
Author(s):  
N. M. Cox ◽  
M. J. Stuart ◽  
T. G. Althen ◽  
W. A. Bennett ◽  
H. W. Miller

2019 ◽  
Vol 26 (8) ◽  
pp. 1025-1033
Author(s):  
Jessica L. Bauer ◽  
Katherine Kuhn ◽  
Andrew P. Bradford ◽  
Zain A. Al-Safi ◽  
Mary A. Harris ◽  
...  

Dietary fish oil restores ovarian function in subfertile rats, which is thought to be associated with decreased transcription of follicle-stimulating hormone (FSH) β-subunit. We have previously demonstrated a reduction in early follicular serum FSH levels in normal weight but not obese women after treatment with omega-3 polyunsaturated fatty acids (PUFA). Herein, we report the effect of supplementation with omega-3 PUFA on urinary reproductive hormones across the whole menstrual cycle. This interventional study included 17 eumenorrheic women, aged 24-41 years. One month of daily morning urine was collected before and after 1 month of omega-3 PUFA supplementation with 4 g of eicosapentaenoic acid and docosahexaenoic acid daily. Measurements included urinary FSH, luteinizing hormone (LH) and estrogen and progesterone metabolites, plasma fatty acid composition, and markers of endoplasmic reticulum stress. Compliance with dietary supplementation was verified by significantly reduced ratios of omega-6 to omega-3 PUFA for all subjects after treatment ( P < .01). After 1 month of omega-3 PUFA supplementation, urinary FSH was significantly decreased in normal weight, but not obese women, in both follicular and luteal phases (−28.4% and −12.6%, respectively, both P = .04). No significant changes were seen in LH or sex steroids for either weight group. The selective and specific decrease in FSH suggests that omega-3 PUFA supplementation merits further investigation in normal weight women with decreased fertility and/or diminished ovarian reserve.


2014 ◽  
Vol 26 (1) ◽  
pp. 171
Author(s):  
M. P. Palhao ◽  
N. S. Junior ◽  
C. R. B. Guimarães ◽  
C. A. C. Fernandes ◽  
M. E. O. Ferreira ◽  
...  

This study aimed to explore changes in follicle diameter and blood flow of the dominant follicle (DF), in ovulation and embryo transfer rates, after inclusion of eCG in a protocol for timed embryo transfer. The effect presence or absence of a corpus luteum (CL) at the start of treatment was also included. Crossbred heifers (n = 116, Bos taurus × Bos indicus), with (n = 61) or without (n = 55) CL, were included in the same hormone protocol: Day 0 (D0), insertion of progesterone (P4) device (1.0 g, Sincrogest®, Ouro Fino, São Paulo, Brazil) and 2 mg of oestradiol benzoato (EB, Sincrodiol®, Ouro Fino); D8, removal of P4 device and injection of sodium Cloprostenol (0.250 mg mL–1, Sincrocio®, Ouro Fino). On D8, the animals with and without CL – at the beginning of the protocol – were equally divided into 2 groups (G): G1 – injection of 300 IU (2.0 mL) of eCG (n = 56; Synchro eCG®, Ouro Fino); G2 – 2.0 mL of saline (n = 60). The ovulations were synchronized with 1 mg of EB on D9. From D8 to D11, the diameter of the DF and blood flow in its wall were recorded daily (M5 ultrasound with colour Doppler technology, 7.5-MHz linear array, DPS medical equipment, São Paulo, Brazil). Approximately 100 frames in colour-flow mode, containing entire cross-sections of the DF, were recorded during each examination. The area of the follicular wall with coloured pixels was measured with ImageJ software (Image Processing and Analysis in Java) from the frame with the largest blood flow signal. Before embryo transfer, all heifers were evaluated, and those with good-quality CL received frozen/thawed embryos (ethylene glycol 1.5 mol). Follicle diameter and blood flow area were compared between groups with or without CL before timed embryo transfer protocol and between eCG treatments. The PROC GLM procedure of SAS (version 9.0) and the t-test were used to assess the differences between means. Pregnancy diagnosis was performed on D35. Embryo transfer (ET) rate of the recipients and pregnancy rate were compared between CL or eCG treatments by the chi-squared test. Ovarian status, before hormone protocol, did not change (P > 0.05) the follicular growth of the DF. However, ovulation rate (78.8 v. 65.4%, P < 0.05) and ET rate (78.7 v. 65.4%, P < 0.05) were higher in animals with CL on D0. From D8 to D10, the inclusion of eCG did not affect (P > 0.05) follicular growth and blood flow of the DF. The time effect (P < 0.0001) for follicular blood flow had shown an increase in area of blood flow 24 h after implant removal (7.7 ± 0.7,b 10.2 ± 0.7,a and 12.3 ± 1.0a mm2, for Days 8, 9, and 10, respectively). The eCG did not affect (P > 0.05) the ovulation rate (71.4 and 73.3%, respectively, eCG and no eCG), however, approached an increased (P < 0.06) ET rate (78.8 v. 66.7%). The overall pregnancy rate (51.2%, 43/84) was not affected (P > 0.05) by evaluated variables. In summary, the addition of 300 IU of eCG on D8 of the timed embryo transfer protocol did not change the development of DF but increased the ET rate of the recipients. Biotran, FAPEMIG (project number APQ-1454-12), and CnPQ are acknowledged.


Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3674-3684 ◽  
Author(s):  
K. A. Walters ◽  
C. M. Allan ◽  
M. Jimenez ◽  
P. R. Lim ◽  
R. A. Davey ◽  
...  

The role of classical genomic androgen receptor (AR) mediated actions in female reproductive physiology remains unclear. Female mice homozygous for an in-frame deletion of exon 3 of the Ar (AR−/−) were subfertile, exhibiting delayed production of their first litter (AR+/+ = 22 d vs. AR−/− = 61 d, P &lt; 0.05) and producing 60% fewer pups/litter (AR+/+: 8.1 ± 0.4 vs. AR−/−: 3.2 ± 0.9, P &lt; 0.01). Heterozygous females (AR+/−) exhibited an age-dependent 55% reduction (P &lt; 0.01) in pups per litter, evident from 6 months of age (P &lt; 0.05), compared with AR+/+, indicating a significant gene dosage effect on female fertility. Ovulation was defective with a significant reduction in corpora lutea numbers (48–79%, P &lt; 0.01) in 10- to 12- and 26-wk-old AR+/− and AR−/− females and a 57% reduction in oocytes recovered from naturally mated AR−/− females (AR+/+: 9.8 ± 1.0 vs. AR−/−: 4.2 ± 1.2, P &lt; 0.01); however, early embryo development to the two-cell stage was unaltered. The delay in first litter, reduction in natural ovulation rate, and aromatase expression in AR+/− and AR−/− ovaries, coupled with the restored ovulation rate by gonadotropin hyperstimulation in AR−/− females, suggest aberrant gonadotropin regulation. A 2.7-fold increase (AR+/+: 35.4 ± 13.4 vs. AR−/−: 93.9 ± 6.1, P &lt; 0.01) in morphologically unhealthy antral follicles demonstrated deficiencies in late follicular development, although growing follicle populations and growth rates were unaltered. This novel model reveals that classical genomic AR action is critical for normal ovarian function, although not for follicle depletion and that haploinsufficiency for an inactivated AR may contribute to a premature reduction in female fecundity.


1992 ◽  
Vol 134 (1) ◽  
pp. 11-18 ◽  
Author(s):  
R. G. Glencross ◽  
E. C. L. Bleach ◽  
B. J. McLeod ◽  
A. J. Beard ◽  
P. G. Knight

ABSTRACT To study the effects of immunoneutralization of endogenous inhibin on gonadotrophin secretion and ovarian function, prepubertal heifers (n = 6) were actively immunized against a synthetic peptide replica of the N-terminal sequence of bovine inhibin α subunit bIα(1–29)Tyr30) coupled to ovalbumin. In contrast to ovalbumin-immunized controls (n=6), bIα(1–29)Tyr30-immunized heifers had detectable inhibin antibody titres (% binding to 125I-labelled bovine inhibin at 1:2000 dilution of plasma) of 17 ± 3% (s.e.m.) at puberty, rising to 31 ± 5% by the end of the study period 7 months later. Neither age (immunized: 295 ± 8 days; controls: 300 ± 5 days) nor body weight (immunized: 254 ± 13 kg; controls 251 ± 9 kg) at onset of puberty differed between groups. Although the difference did not reach statistical significance, mean plasma FSH concentrations recorded in inhibin-immunized heifers remained 35–40% higher than in controls throughout the 12-week period leading up to puberty (P = 0·14) and during nine successive oestrous cycles studied after puberty (P=0·10). Plasma LH concentrations did not differ between groups at any time during the study. Inhibin immunization had no effect on oestrous cycle length (immunized: 19·8±0·5 days; controls: 19·9±0·5 days). However, in comparison with controls, inhibinimmunized heifers had more medium sized (≥0·5 to <1 cm diameter) follicles during both the preovulatory (95%, P<0·001) and post-ovulatory (110%, P < 0·05 waves of follicular growth and more large (>1 cm diameter) follicles during the preovulatory wave (49%, P<0·05). In addition, the number of corpora lutea observed during the post-ovulatory phase of each cycle was significantly greater in the inhibin-immunized group (43%, P<0·01), as was the recorded incidence of cycles with multiple ovulations (19/56 in the inhibin-immunized group compared with 0/54 in controls; P<0·001). All six inhibinimmunized heifers had at least one cycle with multiple ovulation whereas none of the control heifers did so. These results support the conclusion that immunoneutralization of endogenous inhibin using a synthetic peptide-based vaccine can enhance ovarian follicular development and ovulation rate in heifers. Whether this ovarian response is dependent upon the expected increase in secretion of FSH remains to be established. Journal of Endocrinology (1992) 134, 11–18


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