Clinical Outcomes in Patients Receiving Originator Follitropin Alfa and Follitropin Alfa Biosimilars in Real-world Clinical Practice: A Retrospective Study.

Background: Biosimilar drugs have broadened the treatment options in assisted reproductive technology (ART). Real-world data comparing clinical outcomes of originator follitropin alfa (Gonal-f®) with its biosimilars are required to enrich the body of evidence for clinical decision-making on choice of drug. Aims: To compare the ART outcomes in patients receiving originator follitropin (Gonal-f®) and its biosimilars in clinical setting. Settings and Design: Medical records of 364 infertile women who underwent ART between 2016 and 2020 at Akanksha Hospital and Research Institute, Gujrat, India, were retrospectively analysed. Materials and Methods: Participants were divided into two cohorts based on treatment (Gonal-f® cohort; N = 174 and biosimilar cohort; N = 190), each cohort further subdivided into group A (age <35 years) and group B (age ≥35 years). Fresh or frozen embryo transfer was performed as per the standard procedures of the clinic. Pregnancy rates and live birth rate (LBR) were the primary main outcome measures in this study. Statistical Analysis Used: Descriptive statistics and Chi-square test were used for analysis. Results: The number of oocytes retrieved from Gonal-f® and biosimilar cohorts were comparable (13.3 vs. 14.4). Compared to biosimilars, Gonal-f® treatment resulted in higher yield of cleavage stage and blastocyst stage embryos, and the proportion of women with good quality embryos was higher in the Gonal-f® cohort than the biosimilar cohort (83.3% vs. 69.5%). Patients receiving Gonal-f® reported higher pregnancy rates (59.2% vs. 39.7%) and LBR (43% vs. 17.7%) compared to those receiving biosimilars. Conclusions: Gonal-f® (originator follitropin) treatment could result in higher pregnancy rates and LBR in comparison to biosimilars in real-world setting.

Birth of a healthy infant after bone marrow-derived cell therapy.

Bone marrow-derived cell (BMDC) therapy has numerous applications as potential biological cells for use in regenerative medicine. Here, we present an original case of endometrial atrophy associated with genital tuberculosis in a woman who achieved a live birth with BMDC. This 27-year-old woman came to our center with endometrial atrophy and primary infertility. She had a past history of genital tuberculosis and amenorrhea. Her husband's semen quality was normal. The patient was counseled for hysteroscopy due to thin endometrium and advised in vitro fertilization (IVF) with donor eggs in lieu of poor ovarian reserve. Several attempts of IVF with hormone replacement therapy (HRT) were made, but the desired thickness of the endometrium was not achieved. Uterine artery injection of BMDC through interventional radiology was given, followed by HRT for three months, which resulted in improved endometrium. This was subsequently followed by IVF with donor egg. The treatment resulted in the conception and delivery of a 3.1-kg baby boy through lower segment caesarean section with no antenatal, intranatal or postnatal complications. Recently, there has been massive interest in stem cells as a novel treatment method for regenerative medicine, and more specifically for the regeneration of human endometrium disorders like Asherman syndrome and thin endometrium, which was the reason behind using this strategy for treatment.

Drug-free In vitro Activation for Primary Ovarian Insufficiency.

Primary Ovarian Insufficiency (POI) or Diminished Ovarian Reserve (DOR) are the two conditions that affects women leading to infertility due to the lack of follicular growth and ovulation. Egg / Oocyte donation remains an option for these patients. However, with the development in Reproductive medicine various novel technologies like Ovarian Cryopreservation, Fragmentation, in vitro activation with drug treatment or even drug free autotransplantation enables the possibility of activating the pool of primordial follicles that can lead to successful pregnancy outcomes. Here, we report a case of women with POI, in which drug free in vitro activation of follicles was performed, followed by autotransplantation, which resulted in successful pregnancy. This is first case report from India that shows the procedure works and can be tried for women with POI.

A Successful Case for Deselection of Albino Embryo and Live Birth of Albinism-Free Healthy Baby Followed by PGT-M.

In recent years, Preimplantation genetic testing for monogenic disorders (PGT-M) has gained a lot of focus in the field of assisted reproduction technology, various studies have been published in support of it and many are opposing its role. It has been criticized due to many ethical as well as scientific reasons, but there is no doubt that PGT-M has been one of the most important breakthroughs in in vitro fertilization. A critical aspect of this technology is the possibility that the biopsy itself can adversely affect the quality of embryo and compulsion of embryo freezing. Oculocutaneous albinism (OCA) is a condition which is related to skin, hair, eye color (pigments), where affected individuals typically have very fair skin and white- or light-colored hair. These patients are prone to skin cancers on prolonged sun exposure. It also reduces the pigmentation of the colored part of the eyes (the iris) and the light-sensitive tissue at the back of the eye (the retina). People with this condition usually have problem in vision such as reduced sharpness, involuntary eye movements, and photophobia. Here, we report the successful use of PGT-M and a novel protocol for the preimplantation genetic diagnosis of OCA following trophectoderm cell biopsy from blastocysts and the birth of a healthy infant to a couple having previously affected child.

Impact of embryo co-culture with cumulus cells on pregnancy & implantation rate in patients undergoing in vitro fertilization using donor oocyte.

BACKGROUND & OBJECTIVES: Cumulus cell co-culture of embryo had been found to be beneficial for achieving better pregnancy and implantation rate (IR). The present study was aimed to evaluate efficiency of cumulus co-culture technique over simple culture of embryo in terms of pregnancy rate (PR) and IR in patients undergoing treatment for infertility using donor oocytes fertilized by intracytoplasmic sperm injection. METHODS: This was a quasi-experimental study between control and study groups. The primary endpoint was achievement of pregnancy. Control group included 508 women who underwent embryo development without cumulus cell co-culture and study group included 394 women who underwent embryo development with cumulus cell co-culture using donor's cumulus cells. RESULTS: The present study demonstrated a significant increase in the IR (37.2 vs 24.2%, P<0.001) and in PR (45.7 vs 37.8%, P<0.05) in study group than in control group. The PR and IR were found to be higher in study group, among all groups of women, grouped on the basis of different indications for use of donor oocytes. INTERPRETATION & CONCLUSIONS: Cumulus cell co-culture technique was found to be more effective than simple culture technique for embryo development in women undergoing treatment for infertility using donor oocytes fertilized by intracytoplasmic sperm injection.

Embryo genome profiling by single-cell sequencing for successful preimplantation genetic diagnosis in a family harboring COL4A1 c.1537G>A; p.G513S mutation.

CONTEXT: Genetic profiling of embryos (also known as preimplantation genetic diagnosis) before implantation has dramatically enhanced the success quotient of in vitro fertilization (IVF) in recent times. The technology helps in avoiding selective pregnancy termination since the baby is likely to be free of the disease under consideration. AIM: Screening of embryos free from c.1537G>A; p.G513S mutation within the COL4A1 gene for which the father was known in before be in heterozygous condition. SUBJECTS AND METHODS: Processing of trophectoderm biopsies was done from twelve embryos for c.1537G>A; p.G513S mutation within the COL4A1 gene. DNA extracted from isolated cells were subjected to whole genome amplification using an isothermal amplification and strand displacement technology. Oligonucleotide primers bracketing the mutation were synthesized and used to amplify 162 base pairs (bp) polymerase chain reaction amplicons originating from each embryo which were subsequently sequenced to detect the presence or absence of the single base polymorphism. RESULTS: Three out of 12 embryos interrogated in this study were found to be normal while 9 were found to harbor the mutation in heterozygous condition. Implantation of one of the normal embryos following by chorionic villus sampling at 11th week of pregnancy indicated that the baby was free from c.1537G>A; p.G513S mutation within the COL4A1 gene. CONCLUSIONS: Single-cell sequencing is a helpful tool for preimplantation embryo profiling. This is the first report from India describing the birth of a normal child through IVF procedure where a potential pathogenic COL4A1 allele was avoided using this technology.