SAGE Vitrification Kit is intended for use in the vitrification of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

SAGE Vitrification Warming Kit is intended for use in the thawing of virtified oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

Device Description

SAGE Vitrification Kit (ART-8025 and ART-8026): This kit includes two solutions (Equilibration Solution and Vitrification Solutions in the kit consist of a MOPS-buffered media containing non-essential and essential amino acids. gentamicin sulfate, and human serum albumin. These solutions also contain the cryoprotectants ethylene glycol, dimethyl sulfoxide (DMSO) and sucrose as described below:

Equilibration Solution (ES): 7.5% (v/v) each of DMSO and ethylene glycol. Vitrification Solution (VS): 15% (v/v) each of DMSO and ethylene glycol, and 0.6 M sucrose

SAGE Vitrification Warming Kit (ART-8030 and ART 8031): This kit includes three solutions (1.0M Sucrose Warming Solution [1.0 M WS], 0.5M Sucrose Warming Solution [0.5 M WS], and MOPS Solution [MS]). All solutions in the kit consist of a MOPS-buffered media containing non-essential and essential amino acids, gentamicin sulfate, and human serum albumin. These solutions contain the cryoprotectant sucrose at the level described in their names (i.e., 1.0M, 0.5M, or no sucrose).

Solutions in the SAGE Vitrification Kit and SAGE Vitrification Warming Kit are aseptically-filtered and are provided to users in either 5 ml Type 1 borosilicate glass vials with a rubber closure and an aluminum seal (ART-8025 and ART-8030) or 2 ml polypropylene vials with cap (ART-8026 and ART-8031). The solutions in ART-8025 and ART-8030 are single-use only devices, whereas solution in ART-8026 and ART-8031 are to be used within 7 days after opening.

AI/ML Overview

The provided text is a 510(k) summary for the SAGE Vitrification Kit and SAGE Vitrification Warming Kit. It focuses on demonstrating substantial equivalence to a predicate device rather than presenting a study design with acceptance criteria for a new, AI/ML-driven medical device. Therefore, a direct response to your request, which implies an AI/ML device study, is not fully supported by the provided document.

However, I can extract the closest analogous information regarding "acceptance criteria" and "study that proves the device meets the acceptance criteria" from this document as understood within the context of reproductive media and supplements, not AI/ML devices.

Here's a breakdown based on the provided document, interpreting "acceptance criteria" as product specifications and "study" as performance testing and literature review to support substantial equivalence:

1. Table of Acceptance Criteria (Product Specifications) and Reported Device Performance

Parameter	Acceptance Criteria (Subject Device Specification)	Reported Device Performance (Summary)
pH	7.20-7.40	Confirmed by testing (USP<791>).
Osmolality (mOsm/kg)	ES: 2331-2849VS: 5603-68491.0M WS: 1255-15350.5 M WS: 745-911MS: 257-273	Confirmed by testing (USP<785>).
Endotoxin (EU/mL)	<0.5	Confirmed by testing (USP<85>).
MEA 1-cell (% blastocysts at 96h)	≥80%	Confirmed by Mouse Embryo Assay (MEA) 1-Cell.
Sterility	No microbial growth	Confirmed by sterility testing (USP<71>) and Aseptic process validation testing (EN ISO 13408-1:2015 and EN ISO 13408-2:2011).
Shelf-life	52 weeks (ART-8025/8030); 7 days after opening (ART-8026/8031)	ART-8025 and ART-8030 relied on testing from K073522. Real-time shelf-life testing was conducted on ART-8031 to ensure product specifications (Osmolality, Endotoxin, MEA, Sterility) were met at time zero and at 52 weeks (closed and open/simulated use vials). The success of this testing is implied by the conclusion of substantial equivalence.
Clinical Performance (Survival Rates)	Implicit acceptance of effective vitrification and warming for various stages	Oocytes: Literature 1: 94.1%; Literature 2: 75.0%; Literature 4: 92.1%; Literature 5: 90.5%.Pronuclear (PN) Zygotes: Literature 6: 98.6%; Literature 7: 89.0%.Cleavage-Stage Embryos: Literature 8: 97.1%.Collapsed Blastocysts: Literature 9: 98.0%.
Clinical Performance (Fertilization Rates)	Implicit acceptance of effective vitrification and warming for various stages	Oocytes: Literature 1: 67.0%; Literature 2: 77.7%; Literature 5: 64.2%.
Clinical Performance (Pregnancy/Live Birth Rates)	Implicit acceptance of effective vitrification and warming for various stages	Oocytes: Literature 1: Clinical Pregnancy Rate 36.4%; Literature 2: Clinical Pregnancy Rate 33.3%; Literature 3: Pregnancy Rate 33.6%; Literature 4: Clinical Pregnancy Rate per embryo transfer 56.4%, Live Birth Rate per cycle 45.3%; Literature 5: Clinical Pregnancy Rate 40.9%.Pronuclear (PN) Zygotes: Literature 6: Clinical Pregnancy Rate 21.6%; Literature 7: Clinical Pregnancy Rate 28.2%, 9 live birth events (18 infants).Cleavage-Stage Embryos: Literature 8: Clinical Pregnancy Rate 41.6%.Collapsed Blastocysts: Literature 9: Clinical Pregnancy Rate 35.3%.

2. Sample Size Used for the Test Set and Data Provenance

The document does not describe a traditional "test set" in the sense of a dedicated, pre-defined dataset for a single study, as would be done for an AI/ML device. Instead, it relies on a summary of non-clinical performance testing (in-house lab tests) and clinical performance data from published journal articles.

Non-Clinical Test Samples: Not explicitly quantified in terms of sample size (e.g., number of batches, number of media samples tested for pH, osmolality, endotoxin). The Mouse Embryo Assay (MEA) states "1-cell MEA" but doesn't specify the number of mouse embryos or replicate tests.
Clinical Performance Data: This is derived from 9 cited journal articles. The sample sizes vary per study and are reported within the summaries:
- Literature 1: 11 subjects, surplus MII oocytes (quantity not specified).
- Literature 2: 6 subjects, surplus MII oocytes (quantity not specified).
- Literature 3: General results/meta-analysis context, not a specific sample size.
- Literature 4: 2353 MII oocytes.
- Literature 5: 54 study subjects, 413 MII oocytes.
- Literature 6: 37 subjects, 74 embryos.
- Literature 7: 849 pronuclear-stage (PN) zygotes vitrified, 339 PN zygotes thawed over 103 cycles.
- Literature 8: 24 warming cycles (after OHSS risk).
- Literature 9: Control group of 102 warming cycles.
Data Provenance: Not explicitly stated for all studies, but generally refers to clinical studies likely conducted in fertility clinics. The original journal articles (listed in Section XI) would contain this information. Given the context of the device and product development, it is likely these studies were retrospective or prospective clinical trials focusing on IVF outcomes. There is no mention of country of origin for the clinical data within this extract.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This concept is not directly applicable to this type of device (reproductive media). The "ground truth" for non-clinical tests is established by laboratory measurements against predefined product specifications. For the clinical performance, the "ground truth" relates to actual biological outcomes (survival, fertilization, pregnancy, live birth), which are typically reported by clinicians and embryologists involved in the treatment, not "experts establishing ground truth for a test set" in the AI/ML sense. No specific number of experts or their qualifications for establishing ground truth are mentioned.

4. Adjudication Method for the Test Set

Not applicable. There is no "adjudication method" described as one would expect for an AI/ML device's test set. Clinical outcomes are reported as observed, not adjudicated by an independent panel.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

Not applicable. This device is a media kit, not an interpretation tool for image data. Therefore, no MRMC study was performed or described.

6. If a Standalone (Algorithm Only Without Human-in-the Loop Performance) was Done

Not applicable. This is not an AI/ML algorithm. The performance is of the media used by humans in a clinical setting.

7. The Type of Ground Truth Used

Non-Clinical Performance:
- Physical/Chemical Properties: Measured values (pH, Osmolality, Endotoxin) compared to defined ranges.
- Biological Functionality: Mouse Embryo Assay (MEA) results (percentage blastocysts at 96h).
- Sterility: Absence of microbial growth.
Clinical Performance:
- Clinical Outcomes Data: Survival rates, fertilization rates, clinical pregnancy rates, live birth rates following the use of the media in human oocyte/embryo vitrification and warming procedures. This is observational outcomes data from fertility treatments.

8. The Sample Size for the Training Set

Not applicable directly. This is not an AI/ML device that requires a "training set." The development of the media would involve research and formulation, but not in the sense of an AI model's training data.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no "training set" for an AI/ML model for this device. The development of the media relies on cryobiology principles and empirical testing to achieve the desired cryoprotective properties and support oocyte/embryo viability.

Summary

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March 2, 2018

CooperSurgical, Inc % Tove Kjær Director Corporate Regulatory Affairs ORIGIO a/s Knardrupvej 2 DK-2760 Målov Denmark

Re: K173731

Trade/Device Name: SAGE Vitrification Kit (ART-8025 and ART-8026) SAGE Vitrification Warming Kit (ART-8030 and ART-8031) Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: Class II Product Code: MQL Dated: November 23, 2017 Received: December 6, 2017

Dear Tove Kjær:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

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801); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Benjamin R. Fisher -S

Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K173731

Device Name

SAGE Vitrification Kit (ART-8025 and ART-8026) SAGE Vitrification Warming Kit (ART-8030 and ART-8031)

Indications for Use (Describe)

SAGE Vitrification Kit is intended for use in the vitrification of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

SAGE Vitrification Warming Kit is intended for use in the thawing of virtified oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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a CooperSurgical Company

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510(k) SUMMARY K173731

I. Submitter information

Submitted on behalf of: Mr. James Keller Vice President, Regulatory Affairs and Quality Assurance CooperSurgical, Inc. 95 Corporate Drive Trumbull, CT 06611 USA e-mail: James.Keller@coopersurgical.com Phone: +1 (203) - 601 - 5200

Contact person: Ms. Tove Kjær Director Corporate Regulatory Affairs ORIGIO a/s Knardrupvej 2 DK-2760 Måløv Denmark e-mail: tkjaer@origio.com Phone: +45 4679 0220

II. Date prepared March 2, 2018

III. Device Information:

Device name:	SAGE Vitrification Kit (ART-8025 and ART-8026)SAGE Vitrification Warming Kit (ART-8030 and ART-8031)
Common name:	Vitrification Kit and Vitrification Warming Kit
Classification name:	Reproductive media and supplements
Classification Number:	21 CFR 884.6180
Product Code:	MQL (Media, Reproductive)
Regulatory Class:	II

Predicate device: Vit Kit Freeze (Vitrification Freeze Kit) IV. Vit Kit - Thaw (Vitrification Thaw Kit) K160006
The predicate device has not been subject to a design-related recall.

V. Indication for use

SAGE Vitrification Kit is intended for use in the vitrification of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

SAGE Vitrification Warming Kit is intended for use in the thawing of vitrified oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

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VI. Device Description:

SAGE Vitrification Kit (ART-8025 and ART-8026):

This kit includes two solutions (Equilibration Solution and Vitrification Solutions in the kit consist of a MOPS-buffered media containing non-essential and essential amino acids. gentamicin sulfate, and human serum albumin. These solutions also contain the cryoprotectants ethylene glycol, dimethyl sulfoxide (DMSO) and sucrose as described below:

Equilibration Solution (ES): 7.5% (v/v) each of DMSO and ethylene glycol. Vitrification Solution (VS): 15% (v/v) each of DMSO and ethylene glycol, and 0.6 M sucrose

SAGE Vitrification Warming Kit (ART-8030 and ART 8031):

This kit includes three solutions (1.0M Sucrose Warming Solution [1.0 M WS], 0.5M Sucrose Warming Solution [0.5 M WS], and MOPS Solution [MS]). All solutions in the kit consist of a MOPS-buffered media containing non-essential and essential amino acids, gentamicin sulfate, and human serum albumin. These solutions contain the cryoprotectant sucrose at the level described in their names (i.e., 1.0M, 0.5M, or no sucrose).

	Subject device		Predicate device(K160006)		Comparison
Parameter	SAGE VitrificationKitART8025/ART8026	SAGE VitrificationWarming KitART8030/ART8031	Vit-Kit Freeze	Vit-Kit Thaw	N/A
Indication forUse	SAGE VitrificationKit is intended foruse in thevitrification ofoocytes (MII),pronuclear (PN)zygotes throughday 3 cleavagestage embryosand blastocyststage embryos.	SAGEVitrificationWarming Kit isintended for usein the thawing ofoocytes (MII),pronuclear (PN)zygotes throughday 3 cleavagestage embryosand blastocyststage embryos.	Vit Kit-Freeze(VitrificationFreeze Kit) isintended foruse in thevitrification ofoocytes (MII),pronuclear(PN) zygotesthrough day 3cleavage stageembryos andblastocyststage embryos.	Vit Kit- Thaw(VitrificationThaw Kit) isintended foruse in thethawing ofoocytes (MII),pronuclear(PN) zygotesthrough day 3cleavagestageembryos andblastocyststageembryos.	Same
Product and performance specification
pH	7.20-7.40	7.20-7.40	7.05-7.54	7.05-7.44	Different - ThepH range islarger for the
	Subject device		Predicate device(K160006)		Comparison
Parameter	SAGE VitrificationKitART8025/ART8026	SAGE VitrificationWarming KitART8030/ART8031	Vit-Kit Freeze	Vit-Kit Thaw	N/A
					predicatedevices than thesubject devices.Differences in pHdo not raisedifferent Safetyandeffectiveness(S&E) questions.
Osmolality(mOsm/kg)	ES:2331-2849VS:5603-6849	1.0M WS1255-15350.5 M WS745-911MS:257-273	ES:1005-1445VS:1100-1588	TS:1732-1912DS:857-910WS:268-292	Different -Osmolality ishigher in thesubjectvitrification kitsolutions ascompared to thepredicate, whilethe warmingsolutions of thesubject andpredicatedevices aresimilar.Differences inosmolality do notraise differentS&E questions.
Endotoxin(EU/mL)	<0.5	<0.5	≤0.6	≤0.6	Similar
MEA 1-cell (%blastocysts at96h)	≥80%	≥80%	≥80%	≥80%	Same
Sterilization	Aseptic Filtration	Aseptic Filtration	AsepticFiltration	AsepticFiltration	Same
Components
Cryoprotectants	Ethylene glycolDMSOSucrose	Sucrose	Ethylene glycolDMSOSucrose	Sucrose	Same
Amino Acids	Yes	Yes	Yes	Yes	Same
Antibiotics	Gentamicin	Gentamicin	Gentamicin	Gentamicin	Same
Protein	Human SerumAlbumin	Human SerumAlbumin	Dextran SerumSupplement	DextranSerumSupplement	Different -Serum used inthe subject and
	Subject device		Predicate device(K160006)		Comparison
Parameter	SAGE VitrificationKitART8025/ART8026	SAGE VitrificationWarming KitART8030/ART8031	Vit-Kit Freeze	Vit-Kit Thaw	N/A
					predicate mediaare not thesame.Differences inserum do notraise differentquestions ofS&E.
Base medium	Modified HumanTubal Fluid(MOPS-Buffered)	Modified HumanTubal Fluid(MOPS-Buffered)	Medium 199(HEPES-Buffered)	Medium 199(HEPES-Buffered)	Different - Thebase media ofthe subject andpredicate mediaare not thesame.Differences inbase media donot raisedifferentquestions ofS&E.

VII. Comparison of Intended Use and Technological Characteristics of Subject and Predicate Devices

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As noted in the table above, the subject and predicate devices have the same intended use and are technologically comparable. Differences in technological characteristics noted above do not raise different questions of safety or effectiveness.

Summary of Non-Clinical Performance Testing VIII.

The following studies have been performed to support substantial equivalence to the predicate devices:

pH (USP<791>)- 7.2-7.4 .
- Osmolality (USP<785>)

●

o ES: 2331-2849
o VS: 5603-6849
o 1.0 M WS: 1255-1535
o 0.5 M WS: 745-911
o MS: 257-273
Endotoxin testing (USP<85>) <0.5 EU/ml ●
Mouse Embryo Assay (MEA) 1-Cell MEA: ≥80% blastocysts at 96h ●
Aseptic process validation testing meeting the requirements of EN ISO 13408-1:2015 and ● EN ISO 13408-2:2011.
Sterility testing (USP<71>) No microbial growth ●
Shelf-life testing ART-8025 and ART-8030 relied on testing provided in K073522 ● supporting a 52-week shelf-life as the media and media packaging remained unchanged. Real-time shelf-life testing was conducted on ART-8031 to ensure that the following product specifications were met at time zero and at the end of shelf-life (52 weeks) in closed vials and in vials that were opened and underwent simulated use procedures over the seven days prior to testing:

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Osmolality o
Endotoxin o
MEA O
Sterility O

IX. Clinical Performance Data

Published journal articles assessing vitrification and warming media that were identical or similar to the subject devices were provided to support extension of the current indication for vitrifying and warming blastocyst stage embryos to also include vitrification and warming of human MII oocytes, pronuclear (PN) zygotes, and day 3 cleavage-stage embryos. In addition, literature was also provided to support use of the subject media for vitrification and warming of collapsed blastocysts in support of methods included in device labeling. The results included in these studies demonstrated that the subject media was capable of vitrifying and warming the oocytes and embryos as shown by their rates of survival, fertilization, and pregnancy/live birth rates. A summary of the supporting journal articles is shown below:

Oocytes

Literature 1: Reports results after oocvte vitrification/warming using SAGE™ Vitrification Kit . and SAGE™ Vitrification Warming Kit. This study included 11 subjects who had their surplus MII oocytes vitrified. Post-warming results showed a survival rate of 94.1%, fertilization rate of 67.0%, and a clinical pregnancy rate of 36.4%.
Literature 2: Reports results after oocyte vitrification/warming using SAGE™ Vitrification Kit . and SAGE™ Vitrification Warming Kit. The study included six subjects with tubal factor infertility where surplus MII oocytes were vitrified. Post-warming results showed a survival rate of 75.0%, fertilization rate of 77.7%, and a 33.3% clinical pregnancy rate.
Literature 3: The performance of SAGE™ Vitrification Kit and SAGE™ Vitrification Warming . Kit for vitrification and warming of oocytes was shown to be in-line with general results reported after transfer of frozen/thawed oocytes showing a pregnancy rate of 33.6%.
. Literature 4: The control arm in this study used media and vitrification/warming procedures determined to be comparable to the subject devices. Results for subjects in the control arm of this study that assessed outcomes following vitrification and warming of 2353 MII oocytes showed an oocyte survival rate of 92.1%, clinical pregnancy rate per embryo transfer of 56.4%, and a live birth rate per cycle of 45.3%.
Literature 5: This study used media and vitrification procedures determined to be comparable to the subject devices. Clinical oocyte vitrification and warming using a closed vitrification device (54 study subjects and 413 MII oocytes) resulted in a survival rate of 90.5%, fertilization rate of 64.2%, and a clinical pregnancy rate of 40.9%.

Pronuclear (PN) Zygotes

Literature 6: This study assessed the effectiveness of two vitrification and warming media systems. The primary media was determined to be comparable to the subject devices, while the second media assessed was a commercially available media (RapidVit-Cleave) that included different cryoprotectants than the subject devices. Post-warming in the primary media group including 37 subjects and 74 embryos showed a survival rate of 98.6%, with 97% of surviving embryos reaching the cleavage stage. The clinical pregnancy rate was 21.6%. The clinical pregnancy rate for the primary media system was comparable to that observed for the commercially-available comparator media (23.1%).

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Literature 7: This study used media and vitrification procedures determined to be ● comparable to the subject devices. A total of 849 pronuclear-stage (PN) zygotes were vitrified during the study period. During this period. 103 cycles of cryopreserved embryo transfer were completed. In total, 339 PN zygotes were thawed resulting in an 89.0% survival rate. The clinical pregnancy rate obtained was 28.2%, resulting in 9 live birth events (18 infants) with 15 ongoing pregnancies.

Cleavage -Stage Embryos

Literature 8: Reported prospective outcomes following vitrification and warming of cleavage ● stage embryos using the SAGE™ Vitrification Kit and SAGE™ Vitrification Warming Kit. The study included 24 warming cycles after fresh cycle cancellation due to risk of Ovarian Hyperstimulation Syndrome (OHSS). Results showed a post-warming survival rate of 97.1%, a clinical pregnancy rate of 41.6% and an implantation rate of 18.0%.

Vitrification of Collapsed Blastocysts

Literature 9: Reports data after vitrification/warming of collapsed blastocysts generated ● from lower grade cleavage-stage embryos using the SAGE™ Vitrification Kit and SAGE™ Vitrification Warming Kit. Results from the control group (102 warming cycles) in this randomized controlled trial where blastocyst collapse was performed without additional zonal thinning showed a post-warming survival rate of 98.0% and a clinical pregnancy rate of 35.3%.

X. Conclusion

The results of the performance information summarized above demonstrated that the subject devices are as safe and effective as the predicate devices and supports substantial equivalence.

References XI.

1. Pregnancies and deliveries after injection of vitrified-warded oocytes with cryopreserved testicular sperm. (Selman et al, (2010) Fertility and Sterility Vol. 94(7):2927-2929).
1. Ongoing pregnancies after vitrification of human oocytes using a combined solution of ethylene glycol and dimethyl sulfoxide. (Selman et al. (2006) Fertility 86(4):997-1000).
1. Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE. (Kupka et al (2016) Human Reproduction 31(2): 233-248).
1. A combination of hydroxypropyl cellulose and trehalose as supplementation for vitrification of human oocytes: a retrospective cohort study. (Coello et al (2016) Journal of Assisted Reproduction Genetics 33(3): 413-421).
1. Closed vitrification of human oocytes and blastocysts: outcomes from a series of clinical cases. (Gook et al, (2016) J Assist Reprod Genet 33: 1247-1252).
1. Comparison of two different media for vitrification and rewarming of human zygotes: Prospective randomized study. (Alcolak et al, (2011) Middle East Fertility Society Journal 16:189-193).
1. Three years of routine vitrification of human zygotes: is it still fair to advocate slow-rate freezing? (Al-Hasani et al. (2016) Reproductive BioMedicine Online 14(3):288-293).
1. Vitrification is a highly efficient method to cryopreserve human embryos in in-vitro fertilization patients at high risk of developing ovarian hyperstimulation syndrome (Selman et al, (2009) Fertility and Sterility 91(4):1611-1613).
1. Laser-assisted hatching improves clinical outcomes of vitrified-warmed blastocysts developed from low-grade cleavage-stage embryos: a prospective randomized study. (Wan et al, (2014) Reproductive BioMedicine Online 28:582-589).

Regulation Number and Section

§ 884.6180 Reproductive media and supplements.

(a)
Identification. Reproductive media and supplement are products that are used for assisted reproduction procedures. Media include liquid and powder versions of various substances that come in direct physical contact with human gametes or embryos (including water, acid solutions used to treat gametes or embryos, rinsing solutions, sperm separation media, supplements, or oil used to cover the media) for the purposes of preparation, maintenance, transfer or storage. Supplements are specific reagents added to media to enhance specific properties of the media (e.g., proteins, sera, antibiotics, etc.).(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, biocompatibility testing, and clinical testing). The device, when it is phosphate-buffered saline used for washing, and short-term handling and manipulation of gametes and embryos; culture oil used as an overlay for culture media containing gametes and embryos; and water for assisted reproduction applications, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.