265. Gonadotrophic hormones affect the uterus, implantation and fetal development in mice

2005 ◽  
Vol 17 (9) ◽  
pp. 108
Author(s):  
R. L. Kelley ◽  
K. L. Kind ◽  
M. Lane ◽  
R. L. Robker ◽  
J. G. Thompson ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Fetal Development ◽  
Reproductive Tract ◽  
Homeobox Gene ◽  
Chorionic Gonadotrophin ◽  
Leukaemia Inhibitory Factor ◽  
Mrna Levels ◽  
Protein Distribution ◽  
Plasma Progesterone

Although gonadotrophin stimulation using equine chorionic gonadotrophin (eCG) adversely influences pregnancy and fetal development, the effects of stimulation using recombinant human follicle stimulating hormone (rhFSH) are largely unknown. Evidence from human studies indicates that rhFSH may also be detrimental to the endometrium and implantation. We investigated the effect of gonadotrophin stimulation on ovarian hormones and uterine characteristics in the peri-implantation period, and pregnancy outcomes in mice. Adult female mice were stimulated with 2.5 IU or 10 IU rhFSH or 5 IU eCG, followed by 5 IU human chorionic gonadotrophin (hCG). Control mice received saline injections. On day 4 of pseudopregnancy mice either had embryos transferred to the uterus or were sacrificed and blood and uterine samples collected. Plasma progesterone and estradiol concentrations were determined by radioimmunoassay. Uterine mRNA levels of the estrogen and progesterone receptors (ERa and PR), leukaemia inhibitory factor (LIF), homeobox gene Hoxa10 and vascular endothelial growth factor (VEGF) were determined by real-time RT-PCR. Uterine protein distribution of PR was determined by immunohistochemistry. Embryo transfer recipients were sacrificed on day 15 to assess pregnancy outcomes. Gonadotrophin stimulation increased plasma progesterone concentration compared to controls, while estradiol concentrations were not affected. Stimulation also reduced total LIF mRNA and altered the spatial distribution of PR protein in the uterus on day 4. Embryo transfer recipients administered eCG or 10IU rhFSH had lower pregnancy rates compared to controls (11, 35 and 75% respectively) and fetuses from the rhFSH group had reduced mean weight (94 ± 6 v. 176 ± 8 mg), length (11 ± 0.2 v. 12 ± 0.1 mm) and maturity (14.1 ± 0.09 v. 14.6 ± 0.05 days) compared to controls. These results demonstrate that gonadotrophin stimulation induces changes to the maternal reproductive tract prior to implantation that have consequences for the establishment of pregnancy and fetal development in the mouse.

Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study

2021 ◽  
Author(s):  
Manuel Álvarez ◽  
Sofía Gaggiotti-Marre ◽  
Francisca Martínez ◽  
Lluc Coll ◽  
Sandra García ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Luteal Phase ◽  
Frozen Embryo Transfer ◽  
Ongoing Pregnancy ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Group 2 ◽  
Group 1

Abstract STUDY QUESTION Does an individualised luteal phase support (iLPS), according to serum progesterone (P4) level the day prior to euploid frozen embryo transfer (FET), improve pregnancy outcomes when started on the day previous to embryo transfer? SUMMARY ANSWER Patients with low serum P4 the day prior to euploid FET can benefit from the addition of daily subcutaneous P4 injections (Psc), when started the day prior to FET, and achieve similar reproductive outcomes compared to those with initial adequate P4 levels. WHAT IS KNOWN ALREADY The ratio between FET/IVF has spectacularly increased in the last years mainly thanks to the pursuit of an ovarian hyperstimulation syndrome free clinic and the development of preimplantation genetic testing (PGT). There is currently a big concern regarding the endometrial preparation for FET, especially in relation to serum P4 levels around the time of embryo transfer. Several studies have described impaired pregnancy outcomes in those patients with low P4 levels around the time of FET, considering 10 ng/ml as one of the most accepted reference values. To date, no prospective study has been designed to compare the reproductive outcomes between patients with adequate P4 the day previous to euploid FET and those with low, but restored P4 levels on the transfer day after iLPS through daily Psc started on the day previous to FET. STUDY DESIGN, SIZE, DURATION A prospective observational study was conducted at a university-affiliated fertility centre between November 2018 and January 2020 in patients undergoing PGT for aneuploidies (PGT-A) IVF cycles and a subsequent FET under hormone replacement treatment (HRT). A total of 574 cycles (453 patients) were analysed: 348 cycles (leading to 342 euploid FET) with adequate P4 on the day previous to FET, and 226 cycles (leading to 220 euploid FET) under iLPS after low P4 on the previous day to FET, but restored P4 levels on the transfer day. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall we included 574 HRT FET cycles (453 patients). Standard HRT was used for endometrial preparation. P4 levels were measured the day previous to euploid FET. P4 > 10.6 ng/ml was considered as adequate and euploid FET was performed on the following day (FET Group 1). P4 < 10.6 ng/ml was considered as low, iLPS was added in the form of daily Psc injections, and a new P4 analysis was performed on the following day. FET was only performed on the same day when a restored P4 > 10.6 ng/ml was achieved (98.2% of cases) (FET Group 2). MAIN RESULTS AND THE ROLE OF CHANCE Patient’s demographics and cycle parameters were comparable between both euploid FET groups (FET Group 1 and FET Group 2) in terms of age, weight, oestradiol and P4 levels and number of embryos transferred. No statistically significant differences were found in terms of clinical pregnancy rate (56.4% vs 59.1%: rate difference (RD) −2.7%, 95% CI [−11.4; 6.0]), ongoing pregnancy rate (49.4% vs 53.6%: RD −4.2%, 95% CI [−13.1; 4.7]) or live birth rate (49.1% vs 52.3%: RD −3.2%, 95% CI [−12; 5.7]). No significant differences were also found according to miscarriage rate (12.4% vs 9.2%: RD 3.2%, 95% CI [−4.3; 10.7]). LIMITATIONS, REASONS FOR CAUTION Only iLPS through daily Psc was evaluated. The time for Psc injection was not stated and no serum P4 determinations were performed once the pregnancy was achieved. WIDER IMPLICATIONS OF THE FINDINGS Our study provides information regarding an ‘opportunity window’ for improved ongoing pregnancy rates and miscarriage rates through a daily Psc injection in cases of inadequate P4 levels the day previous to FET (P4 < 10.6 ng/ml) and restored values the day of FET (P4 > 10.6 ng/ml). Only euploid FET under HRT were considered, avoiding one of the main reasons of miscarriage and implantation failure and overcoming confounding factors such as female age, embryo quality or ovarian stimulation protocols. STUDY FUNDING/COMPETING INTEREST(S) No external funding was received. B.C. reports personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, IBSA and Gedeon Richter outside the submitted work. N.P. reports grants and personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, Theramex and Besins International and personal fees from IBSA and Gedeon Richter outside the submitted work. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER NCT03740568.

scholarly journals The impact of estradiol on pregnancy outcomes in letrozole-stimulated frozen embryo transfer cycles

F&S Reports ◽  
2021 ◽  
Author(s):  
Wendy Y. Zhang ◽  
Rebecca M. Gardner ◽  
Kristopher I. Kapphahn ◽  
Maya K. Ramachandran ◽  
Gayathree Murugappan ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Frozen Embryo Transfer ◽  
The Impact

scholarly journals NO DIFFERENCE IN IVF OR PREGNANCY OUTCOMES WITH USE OF DIAZEPAM AT TIME OF EMBRYO TRANSFER

2021 ◽  
Vol 116 (1) ◽  
pp. e40
Author(s):  
Fitz VW ◽  
Hammer K ◽  
Souter I ◽  
Bormann C
Keyword(s):  
Embryo Transfer ◽  
Pregnancy Outcomes

Expression of the genes for insulin-like growth factors and their receptors in bone during skeletal growth

1994 ◽  
Vol 267 (2) ◽  
pp. E278-E286 ◽  
Author(s):  
D. D. Bikle ◽  
J. Harris ◽  
B. P. Halloran ◽  
C. T. Roberts ◽  
D. Leroith ◽  
...  
Keyword(s):  
Growth Factors ◽  
Fetal Development ◽  
Skeletal Development ◽  
Skeletal Growth ◽  
Mrna Levels ◽  
Igf I ◽  
Bone Changes ◽  
Rat Bone ◽  
Insulin Like Growth Factors

Insulin-like growth factors (IGF) are important regulators of skeletal growth. To determine whether the capacity to produce and respond to these growth factors changes during skeletal development, we measured the protein and mRNA levels for IGF-I, IGF-II, and their receptors (IGF-IR and IGF-IIR, respectively) in the tibia and femur of rats before and up to 28 mo after birth. The mRNA levels remained high during fetal development but fell after birth, reaching a nadir by 3-6 wk. This fall was most pronounced for IGF-II and IGF-IIR mRNA and least pronounced for IGF-I mRNA. However, after 6 wk, both IGF-I and IGF-IR mRNA levels recovered toward the levels observed at birth. In the prenatal bones, the signals for the mRNAs of IGF-II and IGF-IIR were stronger than the signals for the mRNAs of IGF-I and IGF-IR, although the content of IGF-I was three- to fivefold greater than that of IGF-II. IGF-II levels fell postnatally, whereas the IGF-I content rose after birth such that the ratio IGF-I/IGF-II continued to increase with age. We conclude that, during development, rat bone changes its capacity to produce and respond to IGFs with a progressive trend toward the dominance of IGF-I.

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