Lavima
CAPA-IVM
What is CAPA-IVM?
- CAPA-IVM* is a disruptive new fertility technology.
- CAPA-IVM enables a more natural way of obtaining mature oocytes for IVF and egg freezing without the burden and risks of systemic ovarian stimulation.
- CAPA-IVM aims to provide an alternative safe and effective option for infertile couples, and when seeking oocytes and embryo preservation for future fertility.
* Patented technology
* * Voung et al., Human Reproduction 2020
Principle of CAPA-IVM – Treating the oocyte
Our Aim
Our aim
Our aim is to give women more control about how IVF is performed. As an alternative to conventional IVF, we offer a more natural way of obtaining oocytes for IVF, without the burden and risks of systemic ovarian stimulation with gonadotropins. Our new disruptive technology — CAPA-IVM — requires no hormone stimulation and no trigger, thus avoiding risks and side reactions for the patients.
CAPA-IVM can also be used to preserve fertility in women who have gynecological cancers and would like to preserve their fertility.
In addition, women between 30-34 years who would like to freeze their eggs for future fertility preservation (egg freezing) may use CAPA-IVM to mature their eggs without going through 9–10 days of systemic ovarian stimulation.
Who may benefit from the CAPA-IVM method?
- Infertile women who are in need of fertility treatment and are interested in a safer more natural way without the burden of any systemic ovarian stimulation
- Female cancer patients who are scheduled for chemotherapy or radiation and wishing to preserve their fertility
Physicians
Scientific details of CAPA-IVM
CAPA-IVM – The Technology
The CAPA-IVM technology uses five proprietary components in combination with four media for the pick-up of cumulus-oocyte-complexes (COCs) from 2-8 mm follicles (Collection step), for the search of COCs (Search step), for the capacitation of the oocytes (CAPA Step) and for the in-vitro maturation of the oocytes (IVM step).
The CAPA-IVM procedure includes an extra CAPA culture step of 24 hours followed by the IVM step of 30 hours. In the CAPA step the spontaneous maturation of the COCs is prevented in-vitro through an effective arrest of the meiosis. In addition, cumulus-oocyte gap junctional communication is maintained.
During the procedure, high intrafollicular cAMP levels in the COCs will be retained after oocyte collection during the early phase of the oocyte capacitation.
What is the difference between IVF and CAPA-IVM?
A) Principle of In-vitro Fertilization (IVF) – Treating the patient
In classical IVF, the patient will receive 8–10 days of hormone stimulation with gonadotropins in order to induce the growth of follicles to a size of 12–20 mm. After a hCH trigger, the COCs are then picked up by the gynecologist from the ovaries (oocyte pick-up) and then processed in the embryology lab. After ICSI, embryos are cultured 3 or 5 days at 37 degrees and then on Day 3 or Day 5, one or two embryos will be transferred into the uterus. In the last years more and more labs prefer to culture embryos to Day 5 and vitrify all blastocyst (freeze-all). A single blastocyst is then transferred at a later time point when the endometrium has been synchronized.
B) Principle of CAPA-IVM – Treating the oocyte
In CAPA-IVM, the patient will not receive any hormone stimulation with gonadotropins.
It is also critically important that no hCG trigger will be applied. Immature COCs from unstimulated follicles of 2–8 mm in size are then picked up by the gynecologist from the ovaries. The pick-up procedure is similar to the pick up in IVF. After the oocyte pick up (“Collection Step”), the immature oocytes (COCs) need to be identified and washed. This second step is called “Search Step”. Both the “Collection” and “Search Steps” will be done in the presence of nanomolar concentrations of C-Naturetic Peptide 22 (CNP-22) and Estradiol. The COCs will then undergo a 24 hour culture step, named “CAPA Step” using a special basal media in the presence of CNP-22, and also supplemented with Estradiol FSH and Insulin. In all 3 steps (Collection, Search, CAPA) the spontaneous meiosis of the immature oocytes is prevented and inhibited by CNP. In the 24 hour CAPA Step the cytoplasm is allowed to mature for around 24 hours. The prevention of the spontaneous meiosis and the capacitation of the oocyte for at least 24 hours in the presence of CNP and other important growth factors are critical for the oocyte to acquire the necessary capacity and quality to support the embryo growth after fertilization.
After the CAPA Step, the COCs are washed and placed in a new basal medium, this time supplemented with Amphiregulin, FSH, Insulin and Estradiol. In this IVM step of 30 hours, the meiosis is initiated and fully resumed with the aim of maturing the nucleus, meaning that oocytes will reach the MII stage. The matured oocytes (COCs) are then further processed in the embryology lab. ICSI, embryo culture to Day 5, embryo vitrification and blastocyst transfer to the uterus are done in the same way as in classical IVF.
The main difference between the two approaches is that in CAPA-IVM NO systemic ovarian stimulation is applied and no hCG trigger is needed, while in classical IVF patients undergo up to 10 days of hormone treatment and a hCG trigger is needed. Thus, In CAPA-IVM the oocyte is treated and matured outside the woman’s body, while in classical IVF the patient itself is treated. As a consequence, patients undergoing CAPA-IVM are not confronted with the typical risks and burden of systemic ovarian stimulation.
The CAPA-IVM technology based on C-Natriuretic Peptide has undergone pre-clinical human safety and a number of efficacy trials and its adoption into clinical practice resulted in healthy live birth rates not different from conventional IVF.
WIDER IMPLICATIONS: Over many decades, improvements in clinical IVM have been gradual and incremental. However, in the past few years, landmark discoveries have been made in animal oocyte biology finally making their way into clinical practice leading to improved outcomes for patients. Demonstration of favorable clinical results with CAPA-IVM, as the first clinically tested biphasic IVM system, has led to renewed interest in IVM as an alternative, low-intervention, low-cost, safe, patient-friendly ART approach, especially for patients with PCOS. The same new approach is being used as part of fertility preservation in patients with cancer and holds promise for egg freezing applications for young women wishing to preserve their fertility.
Key Publications in CAPA-IVM
Basic Research
- Romero S, et al.: Immature oocytes from unprimed juvenile mice become a valuable source for embryo production when using c-type natriuretic peptide as essential component of culture medium.
Biol Reprod. 2016;95:64. - Sanchez F, et al.: An improved IVM method for cumulus-oocyte complexes from small follicles in polycystic ovary syndrome patients enhances oocyte competence and embryo yield.
Hum Reprod. 2017;32:2056-68.
Safety Data
- Saenz De Juano MD, et al.: DNA methylation and mRNA expression of imprinted genes in blastocysts derived from an improved IVM method for oocytes from small follicles in PCOS patients.
Hum Reprod. 2019: Aug 9. pii: dez121.
Clinical Trials
Proof-of-concept: standard IVM versus CAPA-IVF (n= 40)
- Sanchez F, et al.: Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles.
Journal of Assist Reprod Genet. 2019 Aug 9. doi: 10.1007/s10815-019-01551-5.
Randomized clinical trial: standard IVM versus CAPA-IVF (n = 80)
- Vuong L. , et al.: Live Births after oocyte in vitro maturation with prematuration step in women with polycystic ovary syndrome.
Journal of Assist Reprod Genet. 2020, 37(2):347-357.
Randomized clinical trial: standard IVF versus CAPA-IVF in ICSI (n = 546)
- Vuong L, et al.: In-vitro maturation of oocytes versus conventional IVF in women with infertility and a high antral follicle count: a randomized non-inferiority controlled trial.
Hum Reprod. 2020 Nov 1;35(11):2537-2547.
Follow up data on babies born using CAPA-IVM
- Nguyen et al.: Development of children born after in vitro maturation with a prematuration step versus natural conception: a prospective cohort study.
J Assist Reprod Genet. 2022, 39 (8): 1959-1965 - Vuong et al.. Development of children born from IVM versus IVF: 2-year follow-up of a randomized controlled trial.
Human Reprod. 2022, 37 (8), 1871-1879
About us
The Board
Prof. Dr. André Rosenthal
President, CEo & Executive Director of lavima
Prof Rosenthal – molecular biologist by training – was member of the leadership group (2015–2017) of Roche Sequencing, a business unit headquartered in California. He was the sole founder and CEO of Signature Diagnostic, a cancer diagnostic company in Germany, which he sold to Roche in 2015. Andre has extensive experience in clinical and experimental cancer research, human genetics and genomics. From 1994 to 2001 he was the head of the German Human Genome Sequencing Project contributing the sequence of chromosome 21. He is a co-founder of Lavima.
Prof. Dr. Johan Smitz
CSO & Executive director of lavima
Prof Smitz – a medical doctor by training – is the head of the Follicle Biology (FOBI) group at the Free University of Brussels (VUB) and member of clinical diagnostics department at University Hospital of VUB (UZ Brussels). Johan has 30 years expertise in Oocyte biology and is worldwide recognized for his expertise. He is a co-founder of Lavima.
Ir Elien Van Hecke
CCO & Executive Director of lavima
Ms Van Hecke is a bioengineer by training and holds a master’s in business economics. She has many years of experience in different marketing and sales roles both in Biotech (Innogenetics) and large diagnostic companies (Fujirebio/Roche Dx). She is a co-founder of Lavima.
Dr. Joan-Carles Arce
CMO Advisor of lavima
Dr. Joan-Carles Arce is the former SVP Global Head of Reproductive Medicine and Maternal Health at Ferring as well es the former CSO of Ferring USA. He has 28 years of drug development experience at Novo Nordisk and Ferring. Joan-Carles can look back on an extensively documented track record of product approvals in the US, Asia and Europe. He is a co-founder of Lavima.
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