REPRODUCTIVE MILESTONES
IVI
IVI was founded in 1990 by Professors José Remohí and Antonio Pellicer and became a leader in fertility treatment in Europe and Latin America.
Its success rates have been one of the best in the sector since its inception, thanks to its continuous efforts in the teaching and research fields, which have put this company on the international vanguard of fertility care.
RMA
RMA was founded in 1999 by Drs. Paul Bergh, Richard Scott and Michael Drews, quickly becoming a leader in reproductive medicine in the United States.
Its success rates were consistently higher than the national average, thanks to cutting-edge research and state-of-the-art technology, and the group was soon recognized as a leader in the Americas.
IVI and RMA
IVI and RMA merged in 2017, a turning point that transformed the assisted reproduction industry, creating the only global company in Europe, the United States and Latin America. The company is expected to finish 2019 with 65 clinics and more than 67,000 assisted reproduction treatments.
IVI and RMA both place great importance on research, high-quality scientific results, and a common culture with a single objective: to achieve the best results for patients.
IVIRMA has been at the forefront of reproductive research. Scientifically, by contributing landmark publications to the literature, and clinically, by being at the vanguard in implementing the most cutting-edge advances in our field.
This is a selection of some of IVIRMA’s most impactful research milestones through the years.
Serum FSH
Follicle-stimulating hormone levels on day 3 of the menstrual cycle are predictive of In Vitro Fertilization (IVF) outcome. Study showed that FSH levels were predictive of IVF outcome. This allowed patients to have a better understanding of their fertility after their initial workup.
Cytoplasmic Transfer
Birth of infant after the transfer of anucleate donor oocyte cytoplasm into recipient eggs. Study showed it is possible to rejuvenate a poor quality egg with young mitochondria from a donor.
Dopamine Agonists in the Prevention of OHSS
Three studies in 2003, 2007, and 2010 (Administration of moderate and high doses of gonadotropins to female rats increases ovarian vascular endothelial growth factor (VEGF) and VEGF receptor-2 expression that is associated to vascular hyperpermeability; Dopamine agonist cabergoline reduces hemoconcentration and ascites in hyperstimulated women undergoing assisted reproduction; and The non-ergot derived dopamine agonist quinagolide in prevention of early ovarian hyperstimulation syndrome in IVF patients: a randomized, double-blind, placebo-controlled trial) first showed that VEGF is associated with the vascular hyperpermeability seen in OHSS and then tested and confirmed that dopamine agonists can be used to prevent the syndrome. Another study in 2011 (Avoiding the use of human chorionic gonadotropin combined with oocyte vitrification and GnRH agonist triggering versus coasting: a new strategy to avoid ovarian hyperstimulation syndrome) showed the efficacy of a GnRH agonist trigger instead of hCG in preventing OHSS.
Endometrioma Removal and Fertility Outcomes
Removal of endometriomas before IVF does not improve fertility outcomes: a matched, case-control study. Study analyzed 189 women with endometriomas undergoing IVF, comparing the outcomes of those who had an ovarian cystectomy prior to treatment to those who did not, and showing no difference in the results of IVF treatment.
Fresh Ovarian Cortex Transplantation
Fresh human orthotopic ovarian cortex transplantation: long-term results. Study showed that fresh orthotopic ovarian cortex transplantation is a viable procedure. It prospectively followed 12 women undergoing the procedure matched to five controls for 2 years, monitoring FSH, AMH, and ovulatory cycles, and showing normal ovarian function after 2 years in 75% of cases.
Obesity and Poor Reproductive Outcomes
Obesity and poor reproductive outcome: the potential role of the endometrium. Study analyzed the outcomes of over 4,000 women undergoing oocyte donation cycles based on their BMI. It showed worse reproductive outcomes in women with a BMI above 25, highlighting the potential role of the endometrium.
Cryotop Vitrification
Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method. Study compared outcomes of fresh and vitrified donor oocytes from the same cycle, demonstrating similar outcomes. This study was instrumental to egg freezing no longer being considered “experimental”.
Impact of Embryo Biopsy Study
Cleavage stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Study showed day 3 embryo biopsy was harmful while day 5 embryo biopsy was not. This showed that a biopsy performed at the blastocyst stage was safe to the embryo and had no untoward effect on IVF outcomes.
Dopamine Agonists for Endometriosis
Two studies in 2009 (Dopamine agonist administration causes a reduction in endometrial implants through modulation of angiogenesis in experimentally induced endometriosis) and 2011 (Dopamine agonist cabergoline reduces hemoconcentration and ascites in hyperstimulated women undergoing assisted reproduction) evaluated the anti-angiogenic effects of dopamine agonists cabergoline and quinagolide and their potential use in the treatment of endometriosis. Studies showed that dopamine agonists could be useful, leading to the development of a quinagolide-ring currently in phase II clinical trials.
Progesterone Levels Affect Outcomes
Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for IVF: analysis of over 4000 cycles. Study revealed that elevated serum progesterone levels on the day of hCG administration is associated with reduced ongoing pregnancy rates, not only demonstrating that elevated progesterone levels can be detrimental, but also establishing a threshold level of progesterone at the time of hCG trigger over which pregnancy rates were decreased.
Vitrification for Oocyte-Banking
Use of cryo-banked oocytes in an ovum donation program: a prospective, randomized, controlled, clinical trial. Study showed that oocyte cryo-storage is effective and clinical pregnancy rates do not differ from fresh oocyte donation. It compared fresh to vitrified oocyte donation, demonstrating the non-inferiority of vitrification and establishing the basis of egg banking.
Comprehensive chromosome screening (CCS) Efficacy Study
Blastocyst biopsy with CCS and fresh embryo transfer significantly increases IVF implantation and delivery rates: a randomized controlled trial. This study showed that CCS helped to improve embryo selection and therefore pregnancy and delivery rates.
Timelapse use for embryo selection
The use of morphokinetics as a predictor of embryo implantation. Study used timelapse incubation technology to incorporate timing of embryo cleavages into a multivariable model to classify embryos based on probability of implantation. This study was followed by many others in which the applications of timelapse for embryo selection were expanded.
Oocyte Vitrification
Oocyte vitrification does not increase the risk of embryonic aneuploidy or diminish the implantation potential of blastocysts created after intracytoplasmic sperm injection: a novel, paired randomized controlled trail using DNA fingerprinting. Study showed that egg freezing did not harm embryos or prevent implantation. This allowed women to pursue egg freezing without fear it would harm their future babies.
B.E.S.T. Trial
IVF with single euploid blastocyst transfer: a randomized controlled trial. Study showed transferring 1 screened embryo instead of 2 unscreened embryos resulted in the same pregnancy rates but with less obstetrical risk to patients. This showed women the benefit of transferring one normal embryo at a time. One embryo = one baby.
Maternal Age
The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosome screening. Study showed that a woman’s eggs produce more abnormal embryos as she ages. This allowed women to understand the mechanisms by which their fertility declines as they age, and plan accordingly.
Genetic compatibility testing
Comprehensive carrier genetic test using next-generation deoxyribonucleic acid sequencing in infertile couples wishing to conceive through assisted reproductive technology. Study used next-generation sequencing to screen prospective parents for many recessive and X-linked gene variants linked to severe childhood phenotypes. This study resulted in the first development of a comprehensive carrier genetic screening test enabling avoidance of transmission of more than 600 diseases.
SuMMIT
Sequential vs. Monophasic Media Impact Trial. A paired randomized controlled trial comparing a sequential media system to a monophasic medium. Study showed growing embryos in multi-step culture was more effective than in single-step culture in our lab. This gave patients peace of mind that their embryos were being grown in the most effective way.
neXgen
Next generation sequencing for embryo selection. Study validated next generation genetic embryo testing platform. This allowed patients to know that the screening platform has undergone rigorous validation and is cutting edge in terms of technology.
The Natural Cycle Study
Characterizing the natural menstrual cycle to determine embryonic aneuploidy. Study showed that IVF without ovarian stimulation led to the same rate of abnormal embryos as stimulated IVF, but with less efficient outcomes. This showed women that their injectable medication was not causing an increase in the number of abnormal embryos.
Oocyte Vitrification vs Ovarian Cortex Transplantation
Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study. Study compared the efficacy of oocyte vitrification with that of ovarian cortex cryopreservation and transplantation in women undergoing gonadotoxic treatments and showed a trend toward higher efficacy of vitrification but no statistical significance, highlighting other differences between both techniques. This is the only publication to date comparing the two methods.
ASCOT Study
Autologous stem cell ovarian transplantation (ASCOT) to increase reproductive potential in patients who are poor responders. Study showed that ASCOT resulted in improvements in antral follicle count and resulted in five pregnancies in 17 patients.
PROV-ET
A prospective, blinded, non-selection study defining the predictive value of abnormal PGT-A results using a targeted amplification-next generation sequencing (NGS) platform. Study showed an error rate of 0-2% in embryos diagnosed as aneuploid and no detrimental effect of embryo biopsy.
Endometriomas and Oocyte Genetics
Single-cell RNA sequencing of oocytes from ovarian endometriosis patients reveals a differential transcriptomic profile associated with lower quality. Study suggested that gene expression in oocytes of women with ovarian endometriosis was affected – reducing oocyte quality –, regardless of whether the oocytes came from the affected ovary or not.
