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Showing posts with label Clinical results in SFC. Show all posts
Showing posts with label Clinical results in SFC. Show all posts

Double stimulation (Duo-OPU)





 —  Continuous stimulation and oocyte retrieval during both the follicular and luteal phases of poor responders in IVF/ICSI programs can increase the obtained oocytes per menstrual cycle




Since the patients with diminished ovarian reserve could spend lots of time, energy, and money, on the multiple IVF treatments, the idea of double stimulation in a single cycle was developed. The following study is to compare the IVF outcomes obtained after single-stimulation (follicular phase stimulation) versus duoble stimulation (during both the follicular and luteal phases) in poor responders in IVF/ICSI programs.






Accordingly, it was believed that more than one follicular wave in a single menstrual cycle:



The retrospective study in Stork Fertility Center involved of total 388 oocytes from 79 patients in which the oocyte-donors were excluded during January to December, 2016. The total of 79 poor responders in IVF/ICSI programs (Bologna Criteria) underwent either duo-stimulation (45 cycles) or single-stimulation (156 cycles).







The mild stimulation 
or nature cycle protocols were used in both the groups,





All the embryos were cultured to blastocyst stage. For those need preimplantation genetic screening (PGS), the blastocysts were biopsied in Day 5 or Day 6. The applied method of PGS includes whole genome amplification following with NGS (Miseq®). The resulted copy number variation analysis was performed on BlueFuse Multi software.




According to the results, the obtained mature oocytes (MII oocytes) per cycle were significant higher in duo-stimulation group (mean 2.83) compare to single-stimulation group (mean 1.53) (p=0.001).





Our data also showed that no significant difference were observed between single-Stimulation and duo-Stimulation in MII rate (81.03%; 83.70%), fertilization rate (72.9%; 73.33%), good embryo rate (74.07%; 69.70%), good blastocyst rate (62.50%; 51.52%), and euploid rate (30.77%; 13.0%). (The data for the PGS in due-stimulation group was limited.)



In conclusion, duo-stimulation statistically significantly increasing the obtained oocytes per menstrual cycle compare to single-stimulation and resulted in similar IVF outcome in patients with reduced ovarian response. Our study suggests this novel stimulation strategy will help poor responders to collect more mature oocytes within a single menstrual cycle.



The abstract was released in the 2017, Asia Pacific Initiative on Reproduction annual congress. (2017 ASPIRE)
小暐 小暐 Author

Double stimulation (Duo-OPU)





 —  Continuous stimulation and oocyte retrieval during both the follicular and luteal phases of poor responders in IVF/ICSI programs can increase the obtained oocytes per menstrual cycle




Since the patients with diminished ovarian reserve could spend lots of time, energy, and money, on the multiple IVF treatments, the idea of double stimulation in a single cycle was developed. The following study is to compare the IVF outcomes obtained after single-stimulation (follicular phase stimulation) versus duoble stimulation (during both the follicular and luteal phases) in poor responders in IVF/ICSI programs.



Accordingly, it was believed that more than one follicular wave in a single menstrual cycle:



The retrospective study in Stork Fertility Center involved of total 388 oocytes from 79 patients in which the oocyte-donors were excluded during January to December, 2016. The total of 79 poor responders in IVF/ICSI programs (Bologna Criteria) underwent either duo-stimulation (45 cycles) or single-stimulation (156 cycles).







The mild stimulation 
or nature cycle protocols were used in both the groups,





All the embryos were cultured to blastocyst stage. For those need preimplantation genetic screening (PGS), the blastocysts were biopsied in Day 5 or Day 6. The applied method of PGS includes whole genome amplification following with NGS (Miseq®). The resulted copy number variation analysis was performed on BlueFuse Multi software.



According to the results, the obtained mature oocytes (MII oocytes) per cycle were significant higher in duo-stimulation group (mean 2.83) compare to single-stimulation group (mean 1.53) (p=0.001).





Our data also showed that no significant difference were observed between single-Stimulation and duo-Stimulation in MII rate (81.03%; 83.70%), fertilization rate (72.9%; 73.33%), good embryo rate (74.07%; 69.70%), good blastocyst rate (62.50%; 51.52%), and euploid rate (30.77%; 13.0%). (The data for the PGS in due-stimulation group was limited.)



In conclusion, duo-stimulation statistically significantly increasing the obtained oocytes per menstrual cycle compare to single-stimulation and resulted in similar IVF outcome in patients with reduced ovarian response. Our study suggests this novel stimulation strategy will help poor responders to collect more mature oocytes within a single menstrual cycle.



The abstract was released in the 2017, Asia Pacific Initiative on Reproduction annual congress. (2017 ASPIRE)






Stork Fertility Center Stork Fertility Center Author

A patient friendly corifollitropin alfa protocol without routine pituitary suppression in normal responders



Author
Huai-Ling Wang1, Hsing-Hua Lai1, Tzu-Hsuan Chuang1, Yu-Wei Shih1, Shih-Chieh Huang1, Meng-Ju Lee1, Shee-Uan Chen2
Affiliation
1Stork Fertility Center, Stork Ladies Clinic, HsinchuTaiwan (R.O.C)
2Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, TaipeiTaiwan (R.O.C)
Publication
Keywords
Corifollitropin alfa;  Controlled ovarian stimulation;  GnRH antagonist












Introduction

Reducing the frequency of injections in an in vitro fertilization (IVF) program is a patient-friendly way to decrease the mental stress and financial burden in infertile couples. The release of corifollitropin alfa simplifies daily injections of short-acting recombinant follicular stimulating hormone (rFSH), and its widely-used protocol involves short-acting gonadotropins supplements and a fixed GnRH antagonist regimen, largely based on follicle size. In this study, the feasibility of corifollitropin alfa without routine pituitary suppression was evaluated, and it may further simplify the injection protocol.


Materials and Methods

Study Design, Size, Duration: A retrospective cohort study was conducted at a private fertility center in Taiwan. Between January 2013 and September 2014, a total of 288 patients were included in the study.
Participants/Materials, Setting, Methods: A total of 288 patients were stimulated by corifollitropin alfa on cycle day 3 following with routine serum hormone monitoring and follicle scanning every other day after 5 days of initial stimulation, and a GnRH antagonist (0.25mg) was only used prophylactically when the luteinizing hormone (LH) was ≧ 6 IU/L (over half of the definitive LH surge). The demographic profile was shown as below:

Results

The incidence of premature LH surge (≧ 10 IU/L) was 2.4% (7/288) before the timely injection of a single GnRH antagonist, and the elevated LH level was dropped down from 11.9 IU/L to 2.2 IU/L after the suppression. The stimulation profile was shown as below:
Two hundred fifty-one patients did not need any antagonist (87.2% [251/288]) throughout the whole stimulation. No adverse effects were observed regarding oocyte competency (fertilization rate: 78%; blastocyst formation rate: 64%). The ongoing pregnancy rate after first cryotransfer is 56.3%, while the final cumulative live birth rate is 69.6%.

Of patients who did and did not receive GnRH antagonist during stimulation, no significant difference existed in their demographics and reproductive outcomes (cumulative live birth rate: 78.4% vs. 68.3%, p=0.35). The comparisons between the patient received GnRH antagonist and those did not during the stimulation were shown as below:

Discussions and Conclusions

The results demonstrated that the routine GnRH antagonist administration is not required in the corifollitropin-alfa cycles using a flexible and hormone-depended antagonist regimen, while the clinical outcome is not compromised. This finding reveals that the use of a GnRH antagonist only occasionally may be needed.
Stork Fertility Center Stork Fertility Center Author

Assessment of corifollitropin alfa for assisted reproduction: a review study

Introduction:
Corifollitropin alfa, a fusion product of recombinant human follicle-stimulating hormone (rFSH) with a hybrid beta subunit C-terminal peptide of human chorionic gonadotropin, plays a similar pharmacologic role as traditional rFSH, but with a longer half life. Clinical applications of corifollitropin alfa in assisted reproductive realm have reported that it stimulates multifollicular growth for 7 days with the same safety and ovarian response as rFSH administration. In 2003, the first report of live birth using corifollitropin alfa stimulation was released in Netherland. In 2010, European union approved corifollitropin alfa in its market, and then Taiwan approved the release of corifollitropin alfa in 2013. To assess the outcomes of corifollitropin alfa in following embryo development of IVF program, including fertilization, good embryo formation (culture to the day 3), and blastocyst formation (culture to the day 5), we analyzed the results generated from the cases stimulating by long-acting rFSH (L-rFSH, corifollitropin alfa) and by traditional rFSH (T-rFSH) shots in this study.

Materials and Methods:
Study Cohort IGeneral patients


A total of 252 cycles were recruited since December, 2012 to September, 2013. There were 91 cycles (average age: 34.9 y/o, range from 28-42) using L-rFSH stimulation (14 cycles with single shots and 77 cycles with T-rFSH supplements), and 161 cycles (average age: 34.9 y/o, range from 23-40) using T-rFSH stimulation, which was set as the control cohort (Table 1). The patients with polycystic ovarian symptoms were excluded from the study cohort. Number of antral follicles, number of retrieval oocyte, hormone levels after stimulating, number of mature oocytes(MII) after retrieving and the fertilization rates were compared between the two groups. Then the good embryo rate (GER) of day3-culture and the good blastocyst rate (GBR) of day5-culture were determined from each group.



Table 1



Study Cohort IIOocyte Donor Cohort
A total of 89 oocyte donating cycles were recruited since December, 2012 to September, 2013. There were 64 cycles using L-rFSH stimulation, and 25 cycles using T-rFSH stimulation, which was set as the control cohort. The same parameters associated with embryo yield were also compared in these two groups.

Treatment Protocol Design
To assess the more friendly protocol to the IVF cases, we designed a protocol with fewer injections based on the traditional rFSH short protocol and the corifollitropin α in GnRH antagonist protocol. The modified protocols were displayed inFigure 1.


Figure 1

Statistics
Statistical evaluations were carried out using nonparametric Student’s t test with Welch’s corrections. The statistical software, prism (http://www.graphpad.com/scientific-software/prism, GraphPad) was administrated in the data processing.

Results
Although the number of antral follicles showed difference between L-rFSH recipients and T-rFSH recipients (10.16±0.44 vs. 8.39±0.31, p<0 .01="" font="" nbsp="">

After oocyte retrieving of L-rFSH recipients and T- rFSH recipients, number of MII oocytes (11.16±0.69 vs. 9.52±0.50, p=0.03), maturation rates (75.8% vs. 78.31%, p=0.16) and fertilization rates (78.72% vs. 77.12%, p=0.26) were no different. In following cultural results of embryos, GER of day3 (61.32% vs. 58.22%, p=0.24) and GBR of day5 (60.39% vs. 57.36%, p=0.21) also performed the similar outcomes from the two groups (Figure 2).


Table 2 General IVF case

After oocyte retrieving of L-rFSH recipients and T- rFSH recipients, number of MII oocytes (11.16±0.69 vs. 9.52±0.50, p=0.03), maturation rates (75.8% vs. 78.31%, p=0.16) and fertilization rates (78.72% vs. 77.12%, p=0.26) were no different. In following cultural results of embryos, GER of day3 (61.32% vs. 58.22%, p=0.24) and GBR of day5 (60.39% vs. 57.36%, p=0.21) also performed the similar outcomes from the two groups (Figure 2).



Figure 2

In the oocyte-donor cohort, the group stimulated by corifollitropin alfa also displayed similar ovarian responses and clinical outcomes in the following embryo culture (Table 3, Figure 3).


Table 3 Oocyte donating cycles


Figure 3

Discussion:
Based on the efficiencies of controlled ovarian stimulation and embryo culture, no significant differences were observed between the recipients of L-rFSH and of T-rFSH. Due to the long lasting effect of corifollitropin alfa, a more patient-friendly option with reduced injective frequencies could be applied to the overseas cases or cases afraid of injections (Table 4, Table 5).


Table 4 Frequency of Injection


Table 5 Cost List

(The study has been published in 2014 Annual Meeting of Taiwanese Obstetrics and Gynecology Society)

References:
1.    A comparison of long-acting FSH versus daily FSH did not show evidence of difference in effect on overall live birth rate or OHSS in 2335 IVF participants (Cochrane Database Syst. Review, 2013)
2.    Long-acting rFSH and short-acting rFSH treatment protocols provided equal success rates of live birth and cumulative pregnancy
(Boostanfar et al., Fertil Steril 2012)
3.    Treatment of poor ovarian responders with corifollitropin α  in a GnRH antagonist protocol results in low pregnancy rates, similarly to conventional stimulation with a short agonist protocol
4.    (Polyzos et al., Fertil Steril 2013)









Stork Fertility Center Stork Fertility Center Author

To make choosing embryo easier - Pre-implantation genetic screening (PGS in Taiwan)




How many embryos do you want to transfer? Which embryo do you want to transfer? Many IVF couples just looked down at the records of the frozen embryos with their puzzled faces, and finally decided to ask the technicians to help them to choose the best embryo for them.



To reduce the risk of multiple birth, such as gestational diabetes, ecplamsia, and premature birth, single embryo transfer (SET) has become more popular in the IVF realm. Specifically, the transferred embryo should be at the blastocyst stage because of its higher implantation rate and higher clinical pregnancy rate. Now the problem comes - how to choose the best blastocyst to be transferred?




According to the released report by Mackay Memorial Hospital in 2013 Annual Meeting of Taiwanese Society of Reproductive Medicine, they found the grading of embryo morphology and the maternal age were two crucial factors to the clinical outcomes through the retrospective study generated by 273 IVF cases recruited from 2009 to 2013. The data has been shown as follows,


Twins
Single
Implantation failure
Number of IVF cases (%)
78 (28.6)
85 (31.3)
110 (40.3)
Age
Grading of embryo morphology (Gardner Criteria)
 Young  ---------------------------- > Old
   Good   ---------------------------- > Poor
Number of retrieved eggsConcentration of oestrodial /progestosteroneAMHThickness of endometriumTiming of the triggered shot
No significant difference

They scored each embryo as following table, and then they transferred one single blastocyst when the total score was over 90. The rate of multiple birth was successfully reduced to 14.3% from 30% by this way.
Score
50
42
35
30
10
Grade
6AA, 5AA, 4AA
4AB, 4BA, 4BB
3AA, 3AB, 3BA, 3BB
4AC, 4BC, 4CB, 3BC, 3CB
4CC, 3CC

Based on this rule, the clinical outcome of single blastocyst transfer (SBT) was displayed,

Number of cases
Clinical pregnancy(%)
Blighted ovum(%)
1st FET
20
14 (70.0%)
3 (21.4%)
2nd FET
4
3  (75.0%)
0 (0%)
Cumulative Pregnancy Rate
85.5%

FET: Frozen-thawed embryo transfer

In the report released by Stork Fertility Center, we related the effect of the grading of embryo morphology and the maternal age with the chromosomal aneuploidy by the aCGH platform.
(Since 2015, we have shifted our PGS platform from aCGH to NGS, which is more robust in the detection of chromosomal mosaicism and segmental aneuploidy).

1.Trophectoderm cell grading: The chromosomal aneuploid rate was significantly higher in grade C embryo than that of grade A or B.

2. The formation rate of blastocyst: The chromosomal aneuploid rate was significantly higher in D6-formed blastocyst than that of D5-formed blastocyst in the group younger 35 years. In the group older than 35 years, the difference was not that obvious.


In conclusion, to evaluate the quality of a blastocyst, three factors were important grading of the embryo, maternal age and the formation rate of blastocyst. Nowadays, the PGS (aCGH) has become more ubiquitous before embryo transferring, and it improves the accuracy of choosing not only the "good-looking" one but also "chromosomal normal" one to be transferred.

References:
Trophectoderm grade predicts outcomes of single-blastocyst transfers. Fertility and Sterility. 2013. 99(5): 1283-1289.

小暐 小暐 Author

To make choosing embryo easier - Pre-implantation genetic screening (PGS in Taiwan)




How many embryos do you want to transfer? Which embryo do you want to transfer? Many IVF couples just looked down at the records of the frozen embryos with their puzzled faces, and finally decided to ask the technicians to help them to choose the best embryo for them.



To reduce the risk of multiple birth, such as gestational diabetes, ecplamsia, and premature birth, single embryo transfer (SET) has become more popular in the IVF realm. Specifically, the transferred embryo should be at the blastocyst stage because of its higher implantation rate and higher clinical pregnancy rate. Now the problem comes - how to choose the best blastocyst to be transferred?




According to the released report by Mackay Memorial Hospital in 2013 Annual Meeting of Taiwanese Society of Reproductive Medicine, they found the grading of embryo morphology and the maternal age were two crucial factors to the clinical outcomes through the retrospective study generated by 273 IVF cases recruited from 2009 to 2013. The data has been shown as follows,


Twins
Single
Implantation failure
Number of IVF cases (%)
78 (28.6)
85 (31.3)
110 (40.3)
Age
Grading of embryo morphology (Gardner Criteria)
 Young  ---------------------------- > Old
   Good   ---------------------------- > Poor
Number of retrieved eggsConcentration of oestrodial /progestosteroneAMHThickness of endometriumTiming of the triggered shot
No significant difference

They scored each embryo as following table, and then they transferred one single blastocyst when the total score was over 90. The rate of multiple birth was successfully reduced to 14.3% from 30% by this way.
Score
50
42
35
30
10
Grade
6AA, 5AA, 4AA
4AB, 4BA, 4BB
3AA, 3AB, 3BA, 3BB
4AC, 4BC, 4CB, 3BC, 3CB
4CC, 3CC

Based on this rule, the clinical outcome of single blastocyst transfer (SBT) was displayed,

Number of cases
Clinical pregnancy(%)
Blighted ovum(%)
1st FET
20
14 (70.0%)
3 (21.4%)
2nd FET
4
3  (75.0%)
0 (0%)
Cumulative Pregnancy Rate
85.5%

FET: Frozen-thawed embryo transfer

In the report released by Stork Fertility Center, we related the effect of the grading of embryo morphology and the maternal age with the chromosomal aneuploidy by the aCGH platform.
(Since 2015, we have shifted our PGS platform from aCGH to NGS, which is more robust in the detection of chromosomal mosaicism and segmental aneuploidy).

1.Trophectoderm cell grading: The chromosomal aneuploid rate was significantly higher in grade C embryo than that of grade A or B.

2. The formation rate of blastocyst: The chromosomal aneuploid rate was significantly higher in D6-formed blastocyst than that of D5-formed blastocyst in the group younger 35 years. In the group older than 35 years, the difference was not that obvious.


In conclusion, to evaluate the quality of a blastocyst, three factors were important grading of the embryo, maternal age and the formation rate of blastocyst. Nowadays, the PGS (aCGH) has become more ubiquitous before embryo transferring, and it improves the accuracy of choosing not only the "good-looking" one but also "chromosomal normal" one to be transferred.

References:
Trophectoderm grade predicts outcomes of single-blastocyst transfers. Fertility and Sterility. 2013. 99(5): 1283-1289.

Stork Fertility Center Stork Fertility Center Author