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Innovations &
Breakthrough in IVF
DR SUNITA ARORA
PART - 3
Proprietary and confidential — do not distribute
Innovations and breakthrough in IVF
Vyjayanthi Srinivasan, Exploring the Latest Trends and Innovations in IVF for 2023, Aug 10.
Genetic
screening
Time-lapse
monitoring
Stem-cell
therapy
Assisted
hatching with
laser technology
Artificial
intelligence
Innovations
in IVF
Proprietary and confidential — do not distribute
Preimplantation Genetic Diagnosis
PGD is an established
reproductive option for couples
with high risk of transmitting
genetic disorders to their baby.
PGD is useful in the diagnosis of a
variety of genetic disorders that
are caused by a known single
gene mutation and chromosome
number or structure
abnormalities, which can be
detected in a single cell.1
PGS for aneuploidy1
• To select euploid embryos
• To select embryos with the
highest chance of
implantation
1. Yan, L et al. Science China. Life sciences, 57(7), 665–671. 2. Casper R et al. F1000Research. 2017;6.
PGD: Preimplantation genetic diagnosis, PGS: Preimplantation genetic screening
PGD may demonstrate abnormal results in more than three-quarters of
embryos tested. The two major reasons are embryo mosaicism and the
trophectoderm sampling technique.2
• Mosaicism of the chromosomal complement in an embryo can be
observed at different stages of embryonic development and is thought
to arise during mitotic cell divisions after fertilization. Mosaic cells might
reside within the inner cell mass, in the trophectoderm, or in both.2
Euploid Mosaic Aneuploid
Proprietary and confidential — do not distribute
Current Indications for PGT
Advanced Maternal
Age
Recurrent Pregnancy
Loss
Repeated Implantation
Failure
Male Factor Infertility
PGT in a Good-
Prognosis Patients
Undergoing Single
Embryo Transfer
PGT-A in Donor Egg
Cycles
PGT for Monogenic
Diseases
Greco E, International Journal of Molecular Sciences. 2020 Jun 19;21(12):4381.
Proprietary and confidential — do not distribute
• Time-lapse monitoring is a continuous monitoring system that allows us to monitor
embryo development in real-time without changes in cultivation conditions.
Favored in –
• The time-lapse device is a specialized incubator with a built-in embryo
monitoring system that takes a photo every 30 minutes in up to 7 focal planes.
• The device creates a time-lapse video of an embryo’s growth, thus allows us to
detect any deviations in the course of embryo development.
Time-lapse monitoring
Repeated unsuccessful
IVF
Embryo has failed to
develop in last cycle
Older women
Sawada Y et al. Evaluation of artificial intelligence using timelapse images of IVF embryos to predict live birth. RBMO VOLUME 43 ISSUE 5 2021
Proprietary and confidential — do not distribute
Reduces The Handling Time Of Embryos
Continuous Real-time Monitoring Of Embryos And
Captures Early Possible Deviations In Development
Helps To Select The Best Quality Embryo For Transfer
Studies have shown that time-lapse embryo monitoring increases
pregnancy success rates by up to 10% compared to traditional
embryo monitoring methods and reduces the total number of cycles
Benefits of time-lapse monitoring
Sawada Y et al. Evaluation of artificial intelligence using timelapse images of IVF embryos to predict live birth. RBMO VOLUME 43 ISSUE 5 2021
Proprietary and confidential — do not distribute
• In recent years, two germline stem cells: “female germ stem cells” (fGSC) or “ovarian stem cells”
(OSCs) were reported to induce ovarian regeneration and a sustained ovarian function.
• White et al. confirmed that mitotically active germ cells from human ovaries, which they named germ
stem cells (GSCs), could be purified and cultured in vitro to form oocytes1
• In addition, injecting stem cells from the BM can stimulate the ovarian function, restore normal
ovarian and hormone levels, and possibly allow pregnancy1
• In 2017, Li et al. found that on days 14, 21, and 28 after transplantation of human umbilical cord
MSCs (UC-MSCs) into rats, the number of follicles improved, the FSH levels decreased, and the
AMH and E2 levels increased, resulting in an increase in the ovarian reserve function2
• At present, stem cell-derived gametes have been used as an in vitro model to evaluate the effects of
drugs. Overall, stem cell research has resulted in important new breakthroughs in the treatment of
infertility.
Stem cell IVF therapy
1. White Y.A., Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat. Med. 2012;18(3):413–421, 2. Li J. Human umbilical cord mesenchymal stem
cells improve the reserve function of perimenopausal ovary via a paracrine mechanism. Stem Cell Res. Ther. 2017;8(1):55
Proprietary and confidential — do not distribute
• Hatching is a pivotal step for successful embryo implantation, where the embryo gets rid of the
ZP. Invitro culture and cryopreservation have shown to thicken the ZP, resulting in the impaired
ability to hatch. Hence the need for Assisted Hatching.
• LAH emerged in 1990’s, and due to its high speed, accuracy and safety, it the most commonly
used method for AH.
• In a study by Wei et al, LAH group was compared to the NLAH group, and significant differences
were noted in the Live birth rate (34.9% v 31.4%), with comparatively similar differences in the
Implantation rate (24.6% v 24.3%),Biochemical pregnancy rate (41.8% v 40.4%), Clinical
pregnancy rate (40.7% v 38.3%).
• In another study by Curfs et al, which showed a statistically significant decrease in miscarriage
rates in couples with females aged 34 or younger (14.9% v 34% in control group) and two or
more previous fresh embryo transfers (13% v 45.9% in control group)
Assisted hatching with laser technology
1.Wei C. Laser-assisted hatching improves pregnancy outcomes in frozen-thawed embryo transfer cycles of cleavage-stage embryos: a large retrospective cohort study with propensity score matching. Journal of Assisted
Reproduction and Genetics. 2023 Feb;40(2):417-27.
2. Curfs MH, A multicentre double-blinded randomized controlled trial on the efficacy of laser-assisted hatching in patients with repeated implantation failure undergoing IVF or ICSI. Human Reproduction. 2023 Oct 1;38(10):1952-60.
Proprietary and confidential — do not distribute
AI in
gamete
selection
AI in embryo
selection
AI in
treatment
regimen
Artificial intelligence in IVF
Artificial intelligence promises a revolutionary change in the field of medicine, including the IVF clinic.
There are, however, major challenges to overcome before AI can take center-stage in IVF treatments.
Chow DJX, Wijesinghe P, Dholakia K, Dunning KR. Does artificial intelligence have a role in the IVF clinic? Reprod Fertil. 2021 Aug 23;2(3):C29-C34. Tadepalli SK, Lakshmi PV. application of
machine learning and artificial intelligence techniques for IVF analysis and prediction. International Journal of Big Data and Analytics in Healthcare (IJBDAH). 2019 Jul 1;4(2):21-33
• Due to scientific and computational growth over the last few
decades, AI has become popular in all areas of technologies
and also has had an impact on medical sciences and clinical
advancement especially where prediction and assessment is
required.
• By applying AI in the field of embryo grading (blastocyst), it
will predict the best embryo which has an accurate outcome
for fertility treatment, which is an automated process without
any human intervention. This has been shown in a study by
Manna et al.
• Similarly, prediction of sperm quality has also been done using
ANN’s with great accuracy, ranging from 70% for the Girela et
al study, to 99.9% for the El-Shafeyi study.
Proprietary and confidential — do not distribute
Choosing the Right
Dydrogesterone
Proprietary and confidential — do not distribute
The innovator Dydrogesterone
with a rich legacy of more than 60 years
could be the right choice for women for
miscarriage management in their most
crucial period
Where life matters…
Mirza F, et al. Genecol Endocrinol. 2016;32(2):97–106.
Proprietary and confidential — do not distribute
Dydrogestone: A breakthrough research from Abbott
CH3
H
H
H
O
3
H C
3
H C H
O
Abbott’s Dydrogesterone:
The first retro-steroid
Progestine in the word1–4
International birth date: 22 April 19601
Currently registered in 110+ markets4
Produced at only one location: Abbott’s
manufacturing plant in Netherlands4
1. Fischer M. Agnew Chem Int Ed Engl 1978;17:16–26.
2. Recurrent Pregnancy Loss. Causes, Controversies, and Treatment. 2nd Edition. CRC Press. 2014. Page 138.
3. Kuhl H. Climacteric. 2005;8(Suppl 1):3–63.
4. Data on file.
MT: Metric Ton.
6-dehydroprogesterone may cause cancer and possible risk of: Impaired fertility and harm to unborn child.1
$: Data on file 1. Information available on https://www.trc-canada.com/prod-img/MSDS/D231520MSDS.pdf Last accessed on 11 Jan 2024
This makes Abbott’s Dydrogesterone the “one” with high purity & standard
Purity is the key parameter to ensure product safety.
Abbott’s dydrogesterone has more stringent quality standards as compared to both Indian &
European Pharmacopoeial limits with not detected levels of impurities$
Abbott’s Dydrogesterone is manufactured with
stringent purity standards
Proprietary and confidential — do not distribute
Attributes of Innovator Dydrogesterone
Abbott is being awarded with the
Certificate of Suitability by
European Pharmacopoeia for
meeting high quality standard for
Dydrogesterone1
Abbott’s Dydrogesterone Generic Dydrogesterone
None
1. Data on file.
No. R0-CEP 2019-114-Revo 00
Name of substance:
1. DYDROGESTEONE
3. Name of holder:
4. ABBOTT HEALTHCARE PRODUCTS B.V.
5. C.J. Van Houtenlaan 36
6. The Netherlands-1381 CP Weesp
More than
600 published studies2
Lack of robust
published evidence2
2. Search results for Duphaston on Pubmed.gov. Available at: https://pubmed.ncbi.nlm.nih.gov/?term=Dydrogesterone%filte=-years.2020-2022. Accessed on: 19 January 2022
** Data on file . ^^ Mirza, et al. Dydrogesteroneuse in early pregnancy. Gynecological Endocrinology, 32:2, 97-106. † In utero exposure of fetuses
~ 100 crore
tablets manufactured
annually at one global
manufacturing site in Weesp,
Netherlands**
Exposure in
> 2
Crore
pregnancies^^,†
Available in
>100
countries**
63+
years of legacy**
Choose Abbott’s Dydrogesterone as it is backed by
Proprietary and confidential — do not distribute
In critical indications like
threatened miscarriage*, recurrent
pregnancy loss#,^ and luteal phase support
in ART1,2
Where life matters…..
Make the right choice of the
Innovator Dydrogesterone!$
*Carp H. Gynecological Endocrinology, 2012; 28(12): 983–990. # Carp H. GynecolEndocrinol, 2015; 31(6): 422–430. ^ Habitual miscarriage $ Data on file
1. Tournaye H, et al. A Phase III randomized controlled trial comparing the ecacy, safety and tolerability of oral dydrogester one versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod.
2017;32(5):1019–1027. 2. Griesinger G, et al. Oral dydrogesteroneversus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod. 2018;33(12):2212–2221
Proprietary and confidential — do not distribute
Summary
Proprietary and confidential — do not distribute
Summary
• IVF Success rates have improved significantly over past decades.
• IVF is a multifactorial procedure that is reliant on proper timing & accuracy.
• Age, ovarian reserve, sperm quality, embryo quality, endometrial receptivity, timing of embryo transfer
influence the success rates of IVF cycles.
• The Implantation window is the time when the endometrium is functionally competent to receive the
embryo. Any displacement in the Window of Implantation can be determined by Endometrial receptivity Array
(ERA).
• Progesterone prepares the endometrium for implantation by bring secretory transformation of the
endometrium.
• Oral dydrogesterone is the preferred progestogen for luteal phase support (LPS) in IVF.
Individualized LPS using additional oral dydrogesterone in patients with low serum progesterone
concentrations has shown to increase the pregnancy rates in Frozen cycles.
• Newer practices such as tailored ovarian stimulation protocols, mild stimulation, elective single embryo
transfer, frozen embryo transfer, blastocyst culture have increased the pregnancy rates.
Proprietary and confidential — do not distribute 26-Mar-24
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Innovations & Breakthrough in IVF PART 3

  • 1. Proprietary and confidential — do not distribute Innovations & Breakthrough in IVF DR SUNITA ARORA PART - 3
  • 2. Proprietary and confidential — do not distribute Innovations and breakthrough in IVF Vyjayanthi Srinivasan, Exploring the Latest Trends and Innovations in IVF for 2023, Aug 10. Genetic screening Time-lapse monitoring Stem-cell therapy Assisted hatching with laser technology Artificial intelligence Innovations in IVF
  • 3. Proprietary and confidential — do not distribute Preimplantation Genetic Diagnosis PGD is an established reproductive option for couples with high risk of transmitting genetic disorders to their baby. PGD is useful in the diagnosis of a variety of genetic disorders that are caused by a known single gene mutation and chromosome number or structure abnormalities, which can be detected in a single cell.1 PGS for aneuploidy1 • To select euploid embryos • To select embryos with the highest chance of implantation 1. Yan, L et al. Science China. Life sciences, 57(7), 665–671. 2. Casper R et al. F1000Research. 2017;6. PGD: Preimplantation genetic diagnosis, PGS: Preimplantation genetic screening PGD may demonstrate abnormal results in more than three-quarters of embryos tested. The two major reasons are embryo mosaicism and the trophectoderm sampling technique.2 • Mosaicism of the chromosomal complement in an embryo can be observed at different stages of embryonic development and is thought to arise during mitotic cell divisions after fertilization. Mosaic cells might reside within the inner cell mass, in the trophectoderm, or in both.2 Euploid Mosaic Aneuploid
  • 4. Proprietary and confidential — do not distribute Current Indications for PGT Advanced Maternal Age Recurrent Pregnancy Loss Repeated Implantation Failure Male Factor Infertility PGT in a Good- Prognosis Patients Undergoing Single Embryo Transfer PGT-A in Donor Egg Cycles PGT for Monogenic Diseases Greco E, International Journal of Molecular Sciences. 2020 Jun 19;21(12):4381.
  • 5. Proprietary and confidential — do not distribute • Time-lapse monitoring is a continuous monitoring system that allows us to monitor embryo development in real-time without changes in cultivation conditions. Favored in – • The time-lapse device is a specialized incubator with a built-in embryo monitoring system that takes a photo every 30 minutes in up to 7 focal planes. • The device creates a time-lapse video of an embryo’s growth, thus allows us to detect any deviations in the course of embryo development. Time-lapse monitoring Repeated unsuccessful IVF Embryo has failed to develop in last cycle Older women Sawada Y et al. Evaluation of artificial intelligence using timelapse images of IVF embryos to predict live birth. RBMO VOLUME 43 ISSUE 5 2021
  • 6. Proprietary and confidential — do not distribute Reduces The Handling Time Of Embryos Continuous Real-time Monitoring Of Embryos And Captures Early Possible Deviations In Development Helps To Select The Best Quality Embryo For Transfer Studies have shown that time-lapse embryo monitoring increases pregnancy success rates by up to 10% compared to traditional embryo monitoring methods and reduces the total number of cycles Benefits of time-lapse monitoring Sawada Y et al. Evaluation of artificial intelligence using timelapse images of IVF embryos to predict live birth. RBMO VOLUME 43 ISSUE 5 2021
  • 7. Proprietary and confidential — do not distribute • In recent years, two germline stem cells: “female germ stem cells” (fGSC) or “ovarian stem cells” (OSCs) were reported to induce ovarian regeneration and a sustained ovarian function. • White et al. confirmed that mitotically active germ cells from human ovaries, which they named germ stem cells (GSCs), could be purified and cultured in vitro to form oocytes1 • In addition, injecting stem cells from the BM can stimulate the ovarian function, restore normal ovarian and hormone levels, and possibly allow pregnancy1 • In 2017, Li et al. found that on days 14, 21, and 28 after transplantation of human umbilical cord MSCs (UC-MSCs) into rats, the number of follicles improved, the FSH levels decreased, and the AMH and E2 levels increased, resulting in an increase in the ovarian reserve function2 • At present, stem cell-derived gametes have been used as an in vitro model to evaluate the effects of drugs. Overall, stem cell research has resulted in important new breakthroughs in the treatment of infertility. Stem cell IVF therapy 1. White Y.A., Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat. Med. 2012;18(3):413–421, 2. Li J. Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism. Stem Cell Res. Ther. 2017;8(1):55
  • 8. Proprietary and confidential — do not distribute • Hatching is a pivotal step for successful embryo implantation, where the embryo gets rid of the ZP. Invitro culture and cryopreservation have shown to thicken the ZP, resulting in the impaired ability to hatch. Hence the need for Assisted Hatching. • LAH emerged in 1990’s, and due to its high speed, accuracy and safety, it the most commonly used method for AH. • In a study by Wei et al, LAH group was compared to the NLAH group, and significant differences were noted in the Live birth rate (34.9% v 31.4%), with comparatively similar differences in the Implantation rate (24.6% v 24.3%),Biochemical pregnancy rate (41.8% v 40.4%), Clinical pregnancy rate (40.7% v 38.3%). • In another study by Curfs et al, which showed a statistically significant decrease in miscarriage rates in couples with females aged 34 or younger (14.9% v 34% in control group) and two or more previous fresh embryo transfers (13% v 45.9% in control group) Assisted hatching with laser technology 1.Wei C. Laser-assisted hatching improves pregnancy outcomes in frozen-thawed embryo transfer cycles of cleavage-stage embryos: a large retrospective cohort study with propensity score matching. Journal of Assisted Reproduction and Genetics. 2023 Feb;40(2):417-27. 2. Curfs MH, A multicentre double-blinded randomized controlled trial on the efficacy of laser-assisted hatching in patients with repeated implantation failure undergoing IVF or ICSI. Human Reproduction. 2023 Oct 1;38(10):1952-60.
  • 9. Proprietary and confidential — do not distribute AI in gamete selection AI in embryo selection AI in treatment regimen Artificial intelligence in IVF Artificial intelligence promises a revolutionary change in the field of medicine, including the IVF clinic. There are, however, major challenges to overcome before AI can take center-stage in IVF treatments. Chow DJX, Wijesinghe P, Dholakia K, Dunning KR. Does artificial intelligence have a role in the IVF clinic? Reprod Fertil. 2021 Aug 23;2(3):C29-C34. Tadepalli SK, Lakshmi PV. application of machine learning and artificial intelligence techniques for IVF analysis and prediction. International Journal of Big Data and Analytics in Healthcare (IJBDAH). 2019 Jul 1;4(2):21-33 • Due to scientific and computational growth over the last few decades, AI has become popular in all areas of technologies and also has had an impact on medical sciences and clinical advancement especially where prediction and assessment is required. • By applying AI in the field of embryo grading (blastocyst), it will predict the best embryo which has an accurate outcome for fertility treatment, which is an automated process without any human intervention. This has been shown in a study by Manna et al. • Similarly, prediction of sperm quality has also been done using ANN’s with great accuracy, ranging from 70% for the Girela et al study, to 99.9% for the El-Shafeyi study.
  • 10. Proprietary and confidential — do not distribute Choosing the Right Dydrogesterone
  • 11. Proprietary and confidential — do not distribute The innovator Dydrogesterone with a rich legacy of more than 60 years could be the right choice for women for miscarriage management in their most crucial period Where life matters… Mirza F, et al. Genecol Endocrinol. 2016;32(2):97–106.
  • 12. Proprietary and confidential — do not distribute Dydrogestone: A breakthrough research from Abbott CH3 H H H O 3 H C 3 H C H O Abbott’s Dydrogesterone: The first retro-steroid Progestine in the word1–4 International birth date: 22 April 19601 Currently registered in 110+ markets4 Produced at only one location: Abbott’s manufacturing plant in Netherlands4 1. Fischer M. Agnew Chem Int Ed Engl 1978;17:16–26. 2. Recurrent Pregnancy Loss. Causes, Controversies, and Treatment. 2nd Edition. CRC Press. 2014. Page 138. 3. Kuhl H. Climacteric. 2005;8(Suppl 1):3–63. 4. Data on file. MT: Metric Ton.
  • 13. 6-dehydroprogesterone may cause cancer and possible risk of: Impaired fertility and harm to unborn child.1 $: Data on file 1. Information available on https://www.trc-canada.com/prod-img/MSDS/D231520MSDS.pdf Last accessed on 11 Jan 2024 This makes Abbott’s Dydrogesterone the “one” with high purity & standard Purity is the key parameter to ensure product safety. Abbott’s dydrogesterone has more stringent quality standards as compared to both Indian & European Pharmacopoeial limits with not detected levels of impurities$ Abbott’s Dydrogesterone is manufactured with stringent purity standards
  • 14. Proprietary and confidential — do not distribute Attributes of Innovator Dydrogesterone Abbott is being awarded with the Certificate of Suitability by European Pharmacopoeia for meeting high quality standard for Dydrogesterone1 Abbott’s Dydrogesterone Generic Dydrogesterone None 1. Data on file. No. R0-CEP 2019-114-Revo 00 Name of substance: 1. DYDROGESTEONE 3. Name of holder: 4. ABBOTT HEALTHCARE PRODUCTS B.V. 5. C.J. Van Houtenlaan 36 6. The Netherlands-1381 CP Weesp More than 600 published studies2 Lack of robust published evidence2 2. Search results for Duphaston on Pubmed.gov. Available at: https://pubmed.ncbi.nlm.nih.gov/?term=Dydrogesterone%filte=-years.2020-2022. Accessed on: 19 January 2022
  • 15. ** Data on file . ^^ Mirza, et al. Dydrogesteroneuse in early pregnancy. Gynecological Endocrinology, 32:2, 97-106. † In utero exposure of fetuses ~ 100 crore tablets manufactured annually at one global manufacturing site in Weesp, Netherlands** Exposure in > 2 Crore pregnancies^^,† Available in >100 countries** 63+ years of legacy** Choose Abbott’s Dydrogesterone as it is backed by
  • 16. Proprietary and confidential — do not distribute In critical indications like threatened miscarriage*, recurrent pregnancy loss#,^ and luteal phase support in ART1,2 Where life matters….. Make the right choice of the Innovator Dydrogesterone!$ *Carp H. Gynecological Endocrinology, 2012; 28(12): 983–990. # Carp H. GynecolEndocrinol, 2015; 31(6): 422–430. ^ Habitual miscarriage $ Data on file 1. Tournaye H, et al. A Phase III randomized controlled trial comparing the ecacy, safety and tolerability of oral dydrogester one versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod. 2017;32(5):1019–1027. 2. Griesinger G, et al. Oral dydrogesteroneversus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod. 2018;33(12):2212–2221
  • 17. Proprietary and confidential — do not distribute Summary
  • 18. Proprietary and confidential — do not distribute Summary • IVF Success rates have improved significantly over past decades. • IVF is a multifactorial procedure that is reliant on proper timing & accuracy. • Age, ovarian reserve, sperm quality, embryo quality, endometrial receptivity, timing of embryo transfer influence the success rates of IVF cycles. • The Implantation window is the time when the endometrium is functionally competent to receive the embryo. Any displacement in the Window of Implantation can be determined by Endometrial receptivity Array (ERA). • Progesterone prepares the endometrium for implantation by bring secretory transformation of the endometrium. • Oral dydrogesterone is the preferred progestogen for luteal phase support (LPS) in IVF. Individualized LPS using additional oral dydrogesterone in patients with low serum progesterone concentrations has shown to increase the pregnancy rates in Frozen cycles. • Newer practices such as tailored ovarian stimulation protocols, mild stimulation, elective single embryo transfer, frozen embryo transfer, blastocyst culture have increased the pregnancy rates.
  • 19. Proprietary and confidential — do not distribute 26-Mar-24 Enter title via "insert>header and footer>footer" | | 19

Editor's Notes

  1. Choosing the best embryo to transfer is crucial, especially when a single embryo transfer program is adopted for different clinical reasons Even young women produce a significant proportion of aneuploid embryos and screening out such abnormalities could potentially increase the efficacy of donor egg (DE) cycles Pre-implantation genetic testing for monogenic diseases (PGT-M) is an advisable approach for couples with the risk of transmitting genetic diseases to their offspring
  2. Let us move on to the final section of discussion on choosing the right Dydrogesterone.
  3. Th innovator Dydrogesterone, with a rich legacy of 60 years should be the right choice for women for miscarriage management in their most crucial period Where life matters…. Reference Mirza FG, Patki A, Pexman-Fieth C. Dydrogesterone use in early pregnancy. Gynecol Endocrinol. 2016;32(2):97–106.
  4. The active pharmaceutical ingredient of Duphaston® is Dydrogesterone, which is a so-called retro-steroid. The structure shows a typical 4-ring system like other steroid hormones, e.g. progesterone; the inverted configuration at C9 and C10 that influences the geometry of the molecule makes it a retro compound. Abott’s Dydrogesterone is the only retro-steroid progestin in the world. 1–3 International birth date: 22 April 1960 (first registration in Luxembourg). Product currently registered in 110+ markets and geographical expansion is ongoing. Product demand grew from few grams to 20+ mt per year in 2019.  Despite all the changes and long history, Dydrogesterone is produced at only ONE location: Abbott Weesp, the Netherlands. Abbott is also the only company that has the know-how to produce Dydrogesterone at an industrial scale and according to European Pharmacopoeia requirements. References Fischer M. Industrial Applications of Photochemical Syntheses. Agnew Chem Int Ed Engl 1978;17:16–26. Recurrent Pregnancy Loss. Causes, Controversies, and Treatment. 2nd Edition. CRC Press. 2014:138. Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005 Aug;8 Suppl 1:3–63.  Internal data on file.