A pharmacogenetic approach to improve low ovarian response by androgens pre-treatment

Author(s):  
Belen Lledo
Author(s):  
E. Scott Sills ◽  
E. Scott Sills ◽  
J. L. Petersen ◽  
N. S. Rickers ◽  
Samuel H. Wood ◽  
...  

This registered, prospective clinical trial assessed serum anti-Mullerian hormone (AMH) patterns after treatment with activated platelet rich plasma (PRP). Patients with low ovarian reserve and/or at least 1 prior failed in vitro fertilization (IVF) cycle (n=182) received PRP injected into ovarian tissue under ultrasound guidance. Pretreatment AMH, BMI and platelet (PLT) concentration were recorded and serum AMH, follicle stimulating hormone, and estradiol were then measured at 2-week intervals for up to three months. Mean±SD patient age was 45.4±6.1yrs. Improved serum AMH was observed in 51 patients (28%) with median increase of 167% [95%CI 91; 280] after treatment; mean interval to maximum AMH increase was 4 weeks (range 2-10 weeks). Improved post-treatment AMH was not limited to younger patients; when stratified by age (<42 vs. ≥42yrs), significant AMH improvements were seen in both groups after treatment (p=0.03 and 0.009, respectively). Among responders, mean basal PLT count was higher (274K) vs. non-responders (250K); p<0.001. This is the first clinical trial to describe an intraovarian PRP technique for low reserve and finds the treatment safe and associated with significant increases in serum AMH for some patients, usually within four weeks. The substantially different pre-treatment PLT concentrations measured across PRP response groups warrants further investigation. Additional research can characterize ovarian response better, optimize PRP protocols, and collect outcomes data from those who subsequently undergo IVF with autologous oocytes.


2009 ◽  
Vol 54 (No. 11) ◽  
pp. 507-516 ◽  
Author(s):  
A. Marton ◽  
V. Faigl ◽  
M. Kerestes ◽  
M. Kulcsar ◽  
S. Nagy ◽  
...  

The ovarian response to a standard chronogest + eCG treatment with plasma levels of insulin, insulin-like growth factor-I (IGF-I), thyroids, non-esterified fatty acids (NEFA), OH-butyrate (BHB) and urea-N (PUN) was studied in lactating Awassi ewes (<i>n</i> = 105) during the late-summer – early autumn transition period. The ewes were inseminated with diluted fresh semen after gestagen removal, and mated thereafter; 26 of them conceived at the fixed-time AI (fix AI; conception rate is calculated from lambing dates). Ovarian function was monitored by milk progesterone (P<sub>4</sub>) profiles. Before synchronization, the ovary was still acyclic in 33 and already cyclic in 72 ewes. Twenty-nine and 43 of the cyclic animals were in the follicular and luteal phases, respectively. After gestagen removal almost all (<i>n</i> = 104) ewes ovulated, although at AI elevated P<sub>4</sub> levels related to the presence of partially luteinized follicles, and short-lived CL-s were observed in 10 and five animals (none of them re-conceived at the fixed time AI). Cycling ewes showed higher insulin and IGF-I levels than the acyclic animals, and those who had not conceived had higher PUN than the pregnant ones. The other metabolic parameters did not differ. Neither conception rate, nor the ovarian response was influenced by the pre-treatment.


1971 ◽  
Vol 68 (2) ◽  
pp. 271-284 ◽  
Author(s):  
W. P. Collins ◽  
E. N. Koullapis ◽  
I. F. Sommerville

ABSTRACT The effect of chlormadinone acetate (6-chloro-17α-hydroxypregna-4,6-diene-3,20-dione-17-acetate) on the secretion and metabolism of progesterone has been investigated in six healthy women. Twenty-four hour urine samples were collected daily throughout pre-treatment cycles and again throughout the second cycle of treatment with 0.5 mg/day chlormadinone acetate. In all urine specimens LH, pregnanediol, oestrone, 17β-oestradiol, and oestriol were determined. Progesterone metabolism was assessed in terms of the transformation of labelled progesterone administered intravenously nine days after the urinary LH peak and progesterone production was calculated from the conversion of labelled hormone to urinary 5β-pregnane-3α,20α-diol glucuroniside and the mass of urinary metabolite of endogenous origin. The results suggested that although the LH peak was markedly suppressed in all subjects (P 0.05 – 0.02; t test), the ovarian response could be divided into two categories. In three individuals, a low but definite premenstrual rise in LH excretion persisted and this was associated with normal or only moderately suppressed progesterone production rates. In addition, there was only a minimal decrease in the level of pregnanediol during the luteal phase of the cycle and in the cyclical excretion of urinary oestrogens. These results are consistent with the luteinisation of a developing follicle without ovulation having necessarily occurred. In the remaining three subjects, the premenstrual rise in LH was not detectable and progesterone production was markedly suppressed. There was no evidence of a rise in pregnanediol in the second half of the cycle in two patients and in the third the level was markedly reduced. In addition, in two of those cycles there was suppression of urinary oestrogen excretion. In treated cycles, there was a significantly lower incorporation of radioactivity into products liberated by solvolysis (P 0.02–0.01; t test). Furthermore, in subjects in whom the progesterone production rate was not markedly suppressed, there was a significant decrease in the conversion of administered progesterone to 5β-pregnane-3α,20α-diol (P 0.01–0.001; t test) and some increase in the conversion to 5α-pregnan-3α-ol-20-one (P 0.02–0.01;t test).


2004 ◽  
Vol 16 (2) ◽  
pp. 233 ◽  
Author(s):  
C. Lopez-Alonso ◽  
T. Encinas ◽  
A. Veiga-Lopez ◽  
R.M. Garcia-Garcia ◽  
J.M. Ros ◽  
...  

In sheep, the injection of a single dose of 1.5mg of the GnRH antagonist Teverelix (Antarelix™, Zentaris, Frankfort, Germany) eliminates large dominant follicles and increases the number of smaller follicles (2–3mm in size) in a short period of time (Lopez-Alonso et al., 2003. Reprod. Abstr. Ser., 30:71). This treatment would be beneficial for increasing the efficiency of ovarian stimulatory protocols, since embryo output is enhanced in the presence of a high number of small follicles, coincidentally with the absence of large follicles, at starting the FSH treatment. However, possible effects of this single high dose of GnRH antagonist on the capacity of follicles to develop in response to FSH treatments has not been determined. In this study, we have characterized patterns of follicular development during a superovulatory treatment with purified ovine FSH (Ovagen™, ICPbio, Auckland, NZ) in sheep treated i.m. with 1.5mg of Antarelix (n=6) or saline (n=4) on Day 9 after the insertion of a progestagen sponge (Chronogest®, Intervet Int, Boxmeer, The Netherlands). Ewes were superovulated with eight decreasing doses (1.5×3, 1.25×2 and 1×3mL) of Ovagen™ injected twice daily from Day 12 of sponge insertion. Number and size of all &gt;2-mm follicles was determined by transrectal ultrasonography just prior to every FSH injection from the first dose to the withdrawal of progestagen sponges. At the start of the gonadotrophin treatment on Day 12, ewes treated with GnRH antagonist showed a higher number of 2–3mm follicles than control ewes (16.2±3.8 v. 5.3±0.3, P&lt;0.05), and a lower number of &gt;4mm follicles (2.2±0.5 v. 5.0±0.6, P&lt;0.01). Thereafter, administration of Ovagen™ induced a significant rise in the number of &gt;4mm follicles at sponge removal in both groups (P&lt;0.0005 for treated ewes and P&lt;0.01 for controls). This number was higher in females treated with GnRH antagonist than in control sheep, although differences did not reach statistical significance (19.3±3.8 v. 12.7±5.4). Current data confirm that administration of a single dose of GnRH antagonist decreases presence of large follicles and increases the number of smaller follicles at the first day of FSH injection. This pre-treatment does not affect competence of follicles to grow in response to superovulatory FSH treatments. Moreover, the number of preovulatory follicles at sponge removal was higher than in untreated ewes. We conclude that the pre-treatment with a single dose of 1.5mg of Antarelix™ on Day 9 of sponge insertion, three days before starting the FSH treatment in a superovulatory protocol, might increase the ovarian response and, thereafter, the yields of follicles.


Author(s):  
E Y. Wang ◽  
J. T. Cherian ◽  
A. Madsen ◽  
R. M. Fisher

Many steel parts are electro-plated with chromium to protect them against corrosion and to improve their wear-resistance. Good adhesion of the chrome plate to the steel surface, which is essential for long term durability of the part, is extremely dependent on surface preparation prior to plating. Recently, McDonnell Douglas developed a new pre-treatment method for chrome plating in which the steel is anodically etched in a sulfuric acid and hydrofluoric acid solution. On carbon steel surfaces, this anodic pre-treatment produces a dark, loosely adhering material that is commonly called the “smut” layer. On stainless steels and nickel alloys, the surface is only darkened by the anodic pre-treatment and little residue is produced. Anodic pre-treatment prior to hard chrome plating results in much better adherence to both carbon and alloy steels.We have characterized the anodic pre-treated steel surface and the resulting “smut” layer using various techniques including electron spectroscopy for chemical analysis (ESCA) on bulk samples and transmission electron microscopy (TEM) and electron energy-loss spectroscopy (EELS) on stripped films.


2021 ◽  
Vol 160 (1) ◽  
pp. 234-243
Author(s):  
Diana Samoil ◽  
Nazek Abdelmutti ◽  
Lisa Ould Gallagher ◽  
Nazlin Jivraj ◽  
Naa Kwarley Quartey ◽  
...  

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