In Vitro Fertilization

SJ04 is a biosimilar of Ovidrel® and is highly similar to Ovidrel®. The purpose of this study was to evaluate the similarity of pharmacokinetics (PK) between recombinant human chorionic gonadotropin injection (SJ04) and Ovidrel® after administration by a single subcutaneous injection in healthy Chinese female subjects. Forty-eight screened healthy female subjects were randomly divided into 2 groups, the T-R group and the R-T group, with 24 subjects in each group. On the morning of the day of administration, they received SJ04 injection or Ovidrel® single subcutaneous injection according to the randomisation table, both at a dose of 250 μg, once per cycle, and crossed over after a washout period.

Our study will include two phases. In Phase I (a retrospective study), archived data will be collected to train the CNN-enhanced MK with RS method on embryo selection, leading to the integrated approach (MK-RS). In Phase II (a prospective study), the integrated MK-RS method established will be used to select embryos, assess the clinical pregnancy rate and evaluate the efficacy of our approach in a randomized controlled trial. In Phase I, images of the embryo will be captured every 10 minutes by the in-built microscope and camera in the time-lapse incubator. Images will then be assessed by the CNN algorithm for day one human embryo segmentation to identify three distinct features: the zona pellucida (ZP), cytoplasm and pronucleus (PN). The morphodynamics of these three features during the fertilisation to first division will be wrapped up as time series data for the integration. The morphology changes after the first division will be semi-auto annotated, which will be analysed by the commercial MK scoring system (KID Score). After removal of embryos/blastocysts from the culture dish, the corresponding spent culture medium (SCM) will be collected in sterile polymerase chain reaction (PCR) tubes. Blank culture mediums will also be collected with the same operating standard. A specifically designed sampler will be used to pipette 7μL SCM of each sample, passing through the oil layer of the SCM, and then drop it onto a disposable quartz glass slide and illuminated by RS system (Basecare Raman 200, China). The RS system will be calibrated to 520.5 cm-1 by silicon wafer before testing. Laser excitation parameters are set as follows: 785 nm wavelength, 320 mW power and 100 μm laser spot diameter. Signals are captured in standard mode with a chargecoupled device (CCD) camera with a 20-seconds integration time. Three replicates will be done for each aliquot. Re-calibration is essential when different culture media is tested, considering that G-1 medium is used for embryos before Day 3 and G-2 medium is used for embryos after Day 3. All obtained spectra will be pre-processed by subtracting the background signal. Spectroscopy signals within the near-infrared region (600 cm-1- 1800 cm-1) are analysed for vector normalisation using Labspec 6 software (Horiba, Japan). Our previous SCM samples with known TE ploidy results will be used as a training dataset to establish euploid-aneuploid classification standards. Stacking classification algorithm will be adopted, considering its high overall accuracy (95.9%, unpublished data). As the segmented time series of CNN algorithm, KID Score annotations and RS profiling results have hundreds of subparameters, we will assemble them together with the ensemble learning, which considers each subparameter as a weak classifier and re-allocated their weights during the training. The primary index for the training is the clinical pregnancy outcome and for the ultimation of the information beneath CNN-enhanced MK and RS, the blastocyst formation results will be used as a secondary index. The ratio of the training set and test set will be 1:1 and in the training set, a 5-fold cross-validation will be performed for monitoring the overfitting. Phase II will comprise a prospective, single-blinded, randomised controlled trial designed to validate the trained MK-RS method for embryo selection. Metabolomic SCM profiling using RS with CNN-enhanced MK analysis will be used to assess embryo developmental potential along with traditional morphological embryo assessments. The embryo developmental potential results will be used to select the best quality of embryos. Sensitivity and specificity will be assessed using the patient's TE biopsy or non-invasive prenatal testing (NIPT) results will further confirm the scoring of MK-RS method, if available. Randomisation: In Phase II, participants who fulfil all the inclusion and exclusion criteria and consent to join the study will be randomised into experimental group and control group in 1 to 1 ratio using a computer-generated randomisation list. For the experimental group, embryo selection will be based on the MK-RS method established in Phase I, whereas embryo selection for the control group will rely on the traditional embryo morphology grading results alone. All participants will be blinded in this trial.

The only additional procedure involves analyzing waste material i.e. cumulus cells by Fertiga nv. RNA is extracted from the cumulus cells and analyzed using qRT-PCR. Cumulus cells iare then assigned to a score based on its RNA levels. This score, known as the Aurora test score, indicates the pregnancy potential of the associated oocyte. Using this evaluation, the embryologist will select the best embryo candidates for transfer. The embryo with the highest Aurora test score from this group will be transferred. If there is no live birth and the trial has not been concluded, the patient may consider frozen/thawed embryo transfer cycles. These consecutive frozen/thawed embryo transfer cycles will also be based on the Aurora test score. The two experimental arms (i.e. fresh SET and frozen/thawed SET) will each include approximately 140 informative patients prospectively recruited for the study undergoing ICSI, with a day 5 blastocyst transfer chosen by embryo morphology and Aurora Test. Taking into account a dropout rate of 40%, 234 patients will be required in each experimental arm. All patients in the experimental arm need to fulfil the inclusion and exclusion criteria as detailed in the protocol. The patients signing the informed consent form (ICF) will have their Cumulus Oocyte complex (COC) numbered at oocyte pick-up (OPU), tracked individually, cumulus cells will be individually denuded and then be snap-frozen and analysed for mRNA expression using oocyte quality predictive genes and two control genes. The RNA expression analysis will be done at Fertiga's Molecular Laboratory. The lab technician/embryologist will track the individual embryos during their growth as usual and classify the embryos based on their routine morphological quality parameters. From the embryos considered for transfer i.e. based on the morphology grading, the one with the highest Aurora Test ranking will be selected for single blastocyst transfer. The study will use two matched historical control groups, each containing 280 patients, resulting in 560 control patients treated within the last 4 years at the Department of Reproductive Medicine of Ghent University Hospital preceding the initiation of the current study (retrospective study cohort). All control patients need to fulfil all the inclusion and exclusion criteria. These control patients will be matched controls where each patient undergoing the Aurora Test will be matched with two patients that had a single embryo transfer based only on morphological grading features. The controls will be matched for stimulation protocol, transfer regime (fresh or frozen/thawed), ovulation trigger (hCG/dual trigger/GnRH agonist), age category (\<31, 31-35, \>35) and for number of good/top quality D5 embryos (2/ 3-4 / 5-6 / \>6).

Despite technical advances in Medically Assisted Reproduction (AMP), the success of fertility treatments is sometimes limited by embryo implantation failure. The coordinated development of the embryo and the uterine endometrium requires close communication between the maternal tissue and the embryo. In in vitro fertilization (IVF), embryo transfer generally takes place between the 2nd (D2) and the 6th (D6) day following oocyte fertilization. Recent studies have shown the advantages of sequential transfer (transfer of an embryo on D2/D3 followed by the transfer of another embryo on D5/D6), with higher implantation and clinical pregnancy rate, fewer miscarriages, more live births, and yet no increase in multiple pregnancies. However, the American Society for Reproductive Medicine recommendations continue to prioritize the transfer of a single embryo for all patients aged under 38. To improve pregnancy rates for patients having a single embryo transferred, the study investigators wish to carry out on "blank" transfer, based on the principle of sequential transfer. The study investigators hypothesize that a culture medium, placed in the uterus before the time of embryo transfer, will modify immune tolerance. The study will test whether transferring the same culture medium in an equivalent quantity as during the real transfer into the uterus 2/3 days before the embryo transfer will improve tolerance to this foreign medium and, therefore, embryo implantation. The aim of this study is thus to evaluate the impact of a "blank" transfer with culture medium alone, on the results of frozen embryo transfers (FET) from IVF.

Infertility is a globally significant medical condition, profoundly impacting individuals and couples both emotionally and physically. The multifaceted nature of in vitro fertilization (IVF) treatment demands active patient participation, with engagement playing a pivotal role in treatment success and satisfaction. However, suboptimal engagement can lead to challenges such as not initiating treatment, missed appointments, medication errors, dropping out and heightened stress levels, all of which may adversely affect clinical outcomes. Recent advancements in Artificial Intelligence (AI) and Machine Learning (ML) have revolutionized healthcare, offering innovative solutions for personalized patient care. In IVF, AI-ML models hold the potential to enhance patient engagement by delivering tailored communication, reminders, and educational support, but also improved prognostication by providing personalized and accurate predictions of treatment outcomes. These capabilities enable patients to make more informed decisions and enhance their adherence to treatment protocols.This protocol outlines a prospective evaluation of an AI-ML model, specifically the Univfy PreIVF report, developed to improve patient engagement in IVF care. Recently, a retrospective, multicenter study reported improved IVF utilization rates among patients counselled using the Univfy PreIVF Report. The current study will prospectively assess the model's effectiveness in addressing individual patient needs and creating a supportive treatment environment. Specifically, this study will measure adherence to providers' recommendation of treatment protocols. By analyzing the impact of these interventions, this research aims to provide robust evidence for the integration of AI-ML technologies in reproductive medicine, paving the way for broader implementation and improved patient outcomes.

This will be a two-arm randomized clinical trial involving more than 100 patients; one arm will undergo superovulation using dosages predicted by the decision support tool, while the other will undergo the current standard treatment. The research question is whether outcomes of patient dosage treatment using Opt-IVF are better or similar to the current practice. We will compare the outcomes of the two groups of patients in terms of the numbers and percentage of mature follicles retrieved at the end of each cycle, total FSH and HMG dosages used, and the number of required testing days for that cycle, total number of M2s, Number of embryos, Number of Grade A embryos and Number of Grade A blastocysts. The trial is for research purposes only. The current tool has not been submitted for any regulatory body approval.

The purpose of this study is to assess the Pharmacokinetic (PK) of Recombinant human follicle-stimulating hormone (follitropin alfa) (r-hFSH) and Recombinant human luteinizing hormone (lutropin alfa) (r-hLH) following a single subcutaneous injection of Pergoveris in pituitary-suppressed healthy female participants of Japanese or Caucasian origin. Study details include: Study Duration: Approximately 9 weeks Treatment Duration: Approximately 4 weeks downregulation with Marvelon® and a single dose of Pergoveris. Visit Frequency: Once in the Screening period, twice in the Downregulation period, and 8 continuous days in the study site during the Confinement period.

This is an observational longitudinal study to advance the understanding of menstrual cycle and gynecologic health conditions including PCOS, infertility and breast cancer.The study will be hosted within the Research app(available on App Store), which allows a user to find, enroll, and participate in Apple-supported health-related research studies.

Female fertility is affected by many factors, such as ovarian function, fallopian tube patency, uterine environment, and mental state, among which the ovaries and endometrium are more important. In reproductive medicine, ovarian dysfunction, poor ovarian reaction, intrauterine adhesion, recurrent implantation failure, and thin endometrium are the five most common diseases that affect fertility. These five diseases lack effective treatment, and previous studies have shown that platelet-rich plasma is promising in treating these five diseases, so it is necessary to further explore the therapeutic effect and potential mechanism.

* Adenomyosis is a benign gynecological disease in which the endometrial stroma invades the uterine myometrium. Adenomyosis affects approximately 10% of women of reproductive age. There are several hypothetical mechanisms in adenomyosis-associated infertility, including dysregulations of the myometrial architecture and function, chronic inflammation, presence of local oxygen, and altered endometrial function, which can cause implantation failure. The abnormal presence of endometrial tissue composed of glands and stroma impacts uterine smooth muscle's regular contractile function and peristalsis, resulting in menometrorrhagia, infertility, and adverse obstetric consequences. There is currently no consensus on the optimal protocol for endometrial preparation in this population, and a lack of data on this issue. Current protocols include routine protocols with or without the pre-treatment of GnRH agonist. However, it is still controversial whether GnRH agonist down-regulation can help patients with adenomyosis have better reproductive outcomes. To our knowledge, there have not been any randomized controlled trials to investigate the effectiveness of the protocols used for endometrial preparation in women with adenomyosis undergoing frozen embryo transfer. * This will be a superiority-designed randomized clinical trial. * This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Vietnam. Potentially eligible women will be provided information about the trial as long as their stimulation cycles are initiated. * Screening for eligibility will be performed by treating physicians on days 2nd - 4th of the menstrual cycle in the subsequent frozen embryo transfer cycles. Patients will be provided a copy of the informed consent documents. Written informed consent will be obtained from all women by the investigator before enrollment. * Women will be randomized (1:1) to either AC (artificial cycle) or GnRHa+AI - AC (Down-Regulation with GnRH agonist and Letrozole combined with artificial cycle) protocols using block randomization with a variable block size of 4, 6, using HOPE Epi with a computer-generated random list. * Artificial cycle (AC): the endometrium will be prepared using oral estradiol valerate (Valiera; Abbott) 6 mg/day starting from the second or fourth day of the menstrual cycle (5). The endometrial thickness will be monitored from the tenth day of estradiol-priming onwards, and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day will be initiated when endometrial thickness reaches 7 mm or more and received oestradiol valerate for at least nine days. Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. Hormonal support will consist of oral estradiol valerate 4 mg/day and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day until the 7th week of gestation. Subsequently, progesterone alone (Cyclogest®; Actavis) at 400 mg twice times a day will be continued for luteal phase support until the 12th week of gestation. \- GnRH agonist + Letrozole - Artificial cycle protocol (GnRHa+AI - AC): * Pre-treatment with GnRH agonist: GnRHa (Triptorelin - Diphereline®, Ipsen, France) will be injected at a dose of 3.75 mg on days 2nd - 4th of menstruation. In addition to GnRHa administration duration, the patients will be indicated letrozole 2.5 mg daily (Femara®, Novartis, Switzerland) to prevent the estradiol flare-up effect from the day of GnRH agonist injection. Repeat the same regimen for the second time 28 days after the first injection of GnRH agonist. * After 55 days of Down Regulation with GnRH agonist, before starting the artificial cycle protocol for endometrial preparation, estradiol serum level will be tested before endometrial preparation. * Endometrial preparation with AC protocol will be started 28 days after the second injection of GnRH agonist, as described previously Frozen embryo transfer: A maximum of 2 cleavage-stage embryos or 1 blastocyst will be thawed on the day of embryo transfer, three or five days after the start of progesterone. Two hours after thawing, surviving embryos will be transferred into the uterus under ultrasound guidance using a soft uterine catheter (Gynétics®, Belgium). \- Future babies' health evaluation and cost-effectiveness analysis will also be performed separately.