scholarly journals Sequential Use of Testosterone Gel and Growth Hormone in Expected Poor Responders and those with Previous Poor Assisted Reproductive Technology Outcomes: A Pilot Study

Author(s):  
Sathya Balasubramanyam

ABSTRACT Introduction Poor responders have suboptimal outcomes following conventional in vitro fertilization/intracytoplasmic sperm injection treatment. There is some evidence that transdermal testosterone and growth hormone may help in improving live birth rates in this group. Aim To present a case series of women who had sequential transdermal testosterone and growth hormone treatment in view of their being expected poor responders or with a history of previous poor oocyte or embryo quality. Setting Private assisted reproduction clinic. Materials and methods A total of 24 women underwent 30 cycles of controlled ovarian stimulation. Ten patients out of 24 had previous poor assisted reproductive technology outcomes, of which 4 were poor responders. Fourteen were expected poor responders. The women used approximately 1.2 gm of transdermal testosterone from day 5 to 25 along with a standard oral contraceptive pill. Growth hormone was given at 8 units/day subcutaneously from day 2 along with the gonadotropins in the antagonist protocol. Results The mean age of the women was 34.92 years (±3.6). The average duration of subfertility was 7.54 (±4.005) years. The mean antral follicle count was 9 (±3.28) and the mean anti-Mullerian hormone level was 1.2 ng/mL (±0.56). The mean number of eggs collected was 8 (±5.45). Number of mature (M2) eggs was 6.6 (±4.5) Mean number of eggs fertilized was 5.04 (±4.03); clinical pregnancy rate was 8/24 (33.3%) and ongoing pregnancy rate was 4/24 (16.6%). Conclusion This case series shows an encouraging clinical pregnancy rate. The reduced ongoing pregnancy rate probably reflects the suboptimal gamete quality. Further randomized controlled trials (RCTs) are needed to assess the efficacy of sequential transdermal testosterone and growth hormone therapy in poor responders. Clinical significance The ongoing pregnancy rate in this group with poor prognosis seems encouraging, and further well-designed RCTs would help in assessing the merits of this sequential therapy. How to cite this article Balasubramanyam S. Sequential Use of Testosterone Gel and Growth Hormone in Expected Poor Responders and those with Previous Poor Assisted Reproductive Technology Outcomes: A Pilot Study. Int J Infertil Fetal Med 2017;8(1):1-4.

Author(s):  
Arie A Polim ◽  
Ivan R Sini ◽  
Indra NC Anwar ◽  
Aryando Pradana ◽  
Kurniawati Kurniawati ◽  
...  

Objective: To investigate the role of CC-highly purified Human Menopausal Gonadotropin (hpHMG) and Growth Hormone (GH) in mini-stimulation protocol to improve outcome in poor ovarian responders (POR). Method: All patients were given clomiphene citrate 150 mg from day 3 to day 7 of menstrual cycle followed by 150 IU hpHMG daily from day 8 until ovulation trigger. Two groups were observed where one group received GH and the other arm did not. In the GH group, 8 IU of GH were given from day 1 of stimulation until stimulation was stopped. GnRH antagonist was used to suppress ovulation. Result: Among 51 eligible women, 29 patients with GH and 22 patients without GH, no difference was observed in the number of oocytes retrieved (2.21 versus 2.64) and the number of embryos transferred (1.24 versus 1.68) in the GH group versus the group without GH, respectively. Total clinical pregnancy rate was 17.6%. No significant difference in pregnancy and ongoing pregnancy rate in both groups (17.2% versus 18.2%) and (13.8% versus 13.6%), respectively. In patients older than 40 years old, GH showed a 4-fold likelihood in producing top quality embryos (44.8% vs 13.6%, OR=3.6, p=0.05). Conclusion: CC-HMG regimen in mini-stimulation protocol is an effective option in poor responders. Additional GH in ministimulation program provided a higher number of top quality embryos in women older than 40 years old, although there were no difference in clinical or ongoing pregnancy rate. Keywords: CC-HMG, growth hormone, IVF, mini-stimulation protocol, poor ovarian responders


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Timotheou ◽  
T Chartomatsidou ◽  
K Kostoglou ◽  
E Papa ◽  
C Ioakeimidou ◽  
...  

Abstract Study question To examine the correlation of first cleavage and blastulation timing on euploidy rates in IVF cycles after PGT-A. Summary answer The timing of blastulation is observed earlier in the euploid embryos. What is known already Embryo evaluation is one of the most critical processes that affect the clinical outcome in IVF cycles. Conventional morphologic assessment and morphokinetic assessment using time lapse technology are performed in order to select the embryo with the higher implantation potential to be transferred. It is stated that embryos with faster developmental potential, especially early forming blastocysts, show increased euploidy rate and higher implantation potential. Study design, size, duration This study includes ICSI/PGT-A treatments completed between May 2018 and December 2019. 117 blastocysts were biopsied and their euploidy status was analyzed by NGS. These embryos resulted from 32 different ICSI treatments. PGT-A was performed due to: a) repeated IVF failure, b) advanced maternal age, c) recurrent pregnancy loss.ICSI was implemented in all cases and blastocysts were vitrified awaiting the genetic results. Single euploid blastocyst transfer followed and clinical pregnancy rate was monitored. Participants/materials, setting, methods Based on the genetic results, the biopsied embryos were divided into two categories; group A representing the euploid embryos and group B the aneuploid embryos. The timing of 1st cleavage and the timing of blastulation, by means of forming a blastocoel, were investigated and compared between the two groups. The rate of early blastocysts in the two groups was also analysed. Early blastocysts are considered those formed at 96h ±2 of embryo culture post ICSI. Main results and the role of chance After the genetic analysis of the biopsied embryos, 37 blastocysts were included in group A-Euploid embryos and 80 blastocysts in group B-Aneuploid embryos. The mean time of the 1st cleavage division was similar between the two groups, with marginally no statistical significance (group A-euploid:25.9h, group B-aneuploid: 26.9h ,p>0.05). Regarding the blastulation time, it was achieved earlier in group A-Euploid, at a mean time of 102.6h, compared to the mean time of 106h in group B-Aneuploid (p < 0.05). Between the cohort of the Euploid embryos (group A), there was a higher rate of early blastulating embryos, compared to the cohort of aneuploid embryos (Group B) (24% VS 17.5%), although it was not statistically significant (p > 0.05). After transferring 1 euploid blastocyst, the ongoing pregnancy rate was monitored in 76.5%, independently of the 1stcleavage and blastulation time of the transferred embryo. Limitations, reasons for caution Further investigation in larger randomized studies is required, as only a limited number of cases were included in this study. Further analysis of the ongoing pregnancy rate between the euploid blastocysts, depending on other morphokinetic parameters would be of paramount significance, as well. Wider implications of the findings: High clinical pregnancy rates observed independently of the analyzed time points, indicate high success rates obtained after PGT-A/NGS. Additionally, success rates show that trophectoderm biopsy is not hazardous for the embryo viability, if performed properly. Concluding, genetic testing combined with time-lapse microscopy may provide further information to improve IVF outcomes. Trial registration number N/A


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
B A Hashimi

Abstract Study question Does exposure of embryos to double vitrification and double warming affect the chances of ongoing pregnancy for patients undergoing PGT-A and transfer euploid embryos? Summary answer Our analysis shows that there is no statistically significant difference in implantation or ongoing pregnancy rate between single or double vitrification/warming cycles. What is known already The use of PGT-A is increasing in the last years and progressively more patients opting in for this, in order to reduce time to pregnancy. Implantation failures prior to genetic testing or the incidence of no-result embryos post PGT-A are some of the scenarios that expose the embryos to multiple rounds of vitrification/warming cycles. The exact effect that such exposure has on embryos is still to be investigated and confirmed as to whether it affects the outcome (i.e. implantation/ongoing pregnancy rate) or the future health of the child. Study design, size, duration Our analysis is a retrospective observation study of data collected from 151 consecutive frozen euploid embryo transfers (FET). These were performed at a single centre between January-December 2020. Two groups were created for this study. The first group includes euploid embryos that were transferred post being exposed to single vitrification/warming (n = 126). In the second group euploid embryos were exposed twice to vitrification/warming (n = 25). Statistical analysis using chi-square test and statistical significance was calculated when p ≤ 0.05. Participants/materials, setting, methods Blastocysts from 151 patients were split into two groups based on the number of vitrification/warming cycles that they underwent prior to FET. The first group includes embryos that were subjected to trophectoderm biopsy and were then vitrified (n = 126). The second group includes embryos that were initially vitrified without undergoing PGT-A analysis. Following implantation failures, their remaining embryos were warmed, biopsied and re-vitrified. Post PGT-A analysis euploid embryos were then re-warmed and transferred (n = 25). Main results and the role of chance For the first group (A), 450 blastocysts (day 5–7) were subjected to trophectoderm biopsy, where 5-cells taken, and embryos were then vitrified. Post PGT-A analysis 260 euploid embryos identified. From them 126 embryos transferred in frozen replacement cycles, where the mean embryo age for the group was 36.1±4.2. The grade of embryos transferred were of 4BC or better based on Gardner’s grading system. The implantation and ongoing pregnancy rate for this group was 62%. For the second group (B), 101 blastocysts (day 5–7) warmed, in order to undergo trophectoderm biopsy and were then re-vitrified. Post PGT-A analysis 49 euploid embryos identified. From them, 25 embryos transferred in frozen replacement cycles, where the mean maternal age for the group was 35.05±5.2. The grade of embryos transferred were of similar quality to group A. The implantation and ongoing pregnancy rate for this group was 64%. Statistical analysis confirmed that there is no statistical difference between the groups (p = 0.74). In addition, 60% of patients (n = 5) who had double vitrification, double biopsy and double warming have ongoing pregnancy. In conclusion, for transferrable quality euploid blastocysts, double vitrification has comparable reproductive outcomes as in single vitrification, thereby supporting the efficacy of double vitrification/warming when necessary. Limitations, reasons for caution This study uses a small sample size of patients. The data are observational and were retrospectively analysed so unknown confounders could not be assessed. The addition of more cycles and further multivariate analysis, including the child’s health is essential for confirmation of the findings. However, initial results are very reassuring. Wider implications of the findings: Our study has implications for clinical practice and patient counselling. Especially in patients that they choose to undergo PGT-A with pre-vitrified embryos post implantation failures with non PGT-A tested embryos. Trial registration number N/A


Author(s):  
Silan Melis Bozan ◽  
Gurkan Bozdag

<p>Poor ovarian response remains one of the major challenges of assisted reproductive technology. Over the years, various interventions have been proposed to improve reproductive outcomes in poor responders, yet few have been shown to be beneficial. Recent studies indicate that hormonal pretreatments might increase clinical pregnancy rate, live birth rate and the number of oocytes retrieved in women with poor ovarian response undergoing assisted reproductive technology. Areas covered: Following extensive research of the up to date literature, this review aims to cover current considerations and controversies regarding the use of hormonal supplements such as dehydroepiandrosterone, transdermal testosterone and growth hormone. Expert opinion: There is limited data for the validity of using growth hormone and androgens or androgen modulating agents during assisted reproductive technology cycles in women suffering from poor ovarian response. However, there is a need to support the available data with further randomized controlled trials seeking for live birth rate as the primary outcome.</p>


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Klaus F. Bühler ◽  
Robert Fischer ◽  
Patrice Verpillat ◽  
Arthur Allignol ◽  
Sandra Guedes ◽  
...  

Abstract Background This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f®) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP®), during assisted reproductive technology (ART) treatments in Germany. Methods Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle). Results Twenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP. Conclusions This large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.


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